The proteome is the entire set of proteins that is, or can be, expressed by a genome, tissue, or organism at a certain time. It is the set of expressed proteins in a given type of cell or organism, at a given time, under defined conditions. Proteomics is the study of the proteome; the term has been applied to several different types of biological systems. A cellular proteome is the collection of proteins found in a particular cell type under a particular set of environmental conditions such as exposure to hormone stimulation, it can be useful to consider an organism's complete proteome, which can be conceptualized as the complete set of proteins from all of the various cellular proteomes. This is roughly the protein equivalent of the genome; the term "proteome" has been used to refer to the collection of proteins in certain sub-cellular biological systems. For example, all of the proteins in a virus can be called a viral proteome. Marc Wilkins coined the term proteome in 1994 in a symposium on "2D Electrophoresis: from protein maps to genomes" held in Siena in Italy.
It appeared in print with the publication of part of his PhD thesis. Wilkins used the term to describe the entire complement of proteins expressed by a genome, tissue or organism; the proteome can be larger than the genome in eukaryotes, as more than one protein can be produced from one gene due to alternative splicing. On the other hand, not all genes are translated to proteins, many known genes encode only RNA, the final functional product. Moreover, complete proteome size vary depending the kingdom of life. For instance, bacteria and viruses have on average 15,145, 3,200, 2,358 and 42 proteins encoded in their genomes; the term “dark proteome" coined by Perdigão and colleagues, defines regions of proteins that have no detectable sequence homology to other proteins of known three-dimensional structure and therefore cannot be modeled by homology. For 546,000 Swiss-Prot proteins, 44–54% of the proteome in eukaryotes and viruses was found to be "dark", compared with only ∼14% in archaea and bacteria.
Numerous methods are available to study sets of proteins, or the whole proteome. In fact, proteins are studied indirectly, e.g. using computational methods and analyses of genomes. Only a few examples are given below. Proteomics, the study of the proteome, has been practiced through the separation of proteins by two dimensional gel electrophoresis. In the first dimension, the proteins are separated by isoelectric focusing, which resolves proteins on the basis of charge. In the second dimension, proteins are separated by molecular weight using SDS-PAGE; the gel is dyed with silver to visualize the proteins. Spots on the gel are proteins. Mass spectrometry has augmented proteomics. Peptide mass fingerprinting identifies a protein by cleaving it into short peptides and deduces the protein's identity by matching the observed peptide masses against a sequence database. Tandem mass spectrometry, on the other hand, can get sequence information from individual peptides by isolating them, colliding them with a non-reactive gas, cataloguing the fragment ions produced.
In May 2014, a draft map of the human proteome was published in Nature. This map was generated using high-resolution Fourier-transform mass spectrometry; this study profiled 30 histologically normal human samples resulting in the identification of proteins coded by 17,294 genes. This accounts for around 84% of the total annotated protein-coding genes. Protein fragment complementation assays are used to detect protein–protein interactions; the yeast two-hybrid assay is the most popular of them but there are numerous variations, both used in vitro and in vivo. Metabolome Cytome Bioinformatics List of omics topics in biology Plant Proteome Database Transcriptome Interactome Human Proteome Project BioPlex PIR database UniProt database Pfam database at the Library of Congress Web Archives
Membrane potential is the difference in electric potential between the interior and the exterior of a biological cell. With respect to the exterior of the cell, typical values of membrane potential given in millivolts, range from –40 mV to –80 mV. All animal cells are surrounded by a membrane composed of a lipid bilayer with proteins embedded in it; the membrane serves as a diffusion barrier to the movement of ions. Transmembrane proteins known as ion transporter or ion pump proteins push ions across the membrane and establish concentration gradients across the membrane, ion channels allow ions to move across the membrane down those concentration gradients. Ion pumps and ion channels are electrically equivalent to a set of batteries and resistors inserted in the membrane, therefore create a voltage between the two sides of the membrane. All plasma membranes have an electrical potential across them, with the inside negative with respect to the outside; the membrane potential has two basic functions.
First, it allows a cell to function as a battery, providing power to operate a variety of "molecular devices" embedded in the membrane. Second, in electrically excitable cells such as neurons and muscle cells, it is used for transmitting signals between different parts of a cell. Signals are generated by opening or closing of ion channels at one point in the membrane, producing a local change in the membrane potential; this change in the electric field can be affected by either adjacent or more distant ion channels in the membrane. Those ion channels can open or close as a result of the potential change, reproducing the signal. In non-excitable cells, in excitable cells in their baseline states, the membrane potential is held at a stable value, called the resting potential. For neurons, typical values of the resting potential range from –70 to –80 millivolts; the opening and closing of ion channels can induce a departure from the resting potential. This is called a depolarization if the interior voltage becomes less negative, or a hyperpolarization if the interior voltage becomes more negative.
In excitable cells, a sufficiently large depolarization can evoke an action potential, in which the membrane potential changes and for a short time reversing its polarity. Action potentials are generated by the activation of certain voltage-gated ion channels. In neurons, the factors that influence the membrane potential are diverse, they include numerous types of ion channels, some of which are chemically gated and some of which are voltage-gated. Because voltage-gated ion channels are controlled by the membrane potential, while the membrane potential itself is influenced by these same ion channels, feedback loops that allow for complex temporal dynamics arise, including oscillations and regenerative events such as action potentials; the membrane potential in a cell derives from two factors: electrical force and diffusion. Electrical force arises from the mutual attraction between particles with opposite electrical charges and the mutual repulsion between particles with the same type of charge.
Diffusion arises from the statistical tendency of particles to redistribute from regions where they are concentrated to regions where the concentration is low. Voltage, synonymous with difference in electrical potential, is the ability to drive an electric current across a resistance. Indeed, the simplest definition of a voltage is given by Ohm's law: V=IR, where V is voltage, I is current and R is resistance. If a voltage source such as a battery is placed in an electrical circuit, the higher the voltage of the source the greater the amount of current that it will drive across the available resistance; the functional significance of voltage lies only in potential differences between two points in a circuit. The idea of a voltage at a single point is meaningless, it is conventional in electronics to assign a voltage of zero to some arbitrarily chosen element of the circuit, assign voltages for other elements measured relative to that zero point. There is no significance in which element is chosen as the zero point—the function of a circuit depends only on the differences not on voltages per se.
However, in most cases and by convention, the zero level is most assigned to the portion of a circuit, in contact with ground. The same principle applies to voltage in cell biology. In electrically active tissue, the potential difference between any two points can be measured by inserting an electrode at each point, for example one inside and one outside the cell, connecting both electrodes to the leads of what is in essence a specialized voltmeter. By convention, the zero potential value is assigned to the outside of the cell and the sign of the potential difference between the outside and the inside is determined by the potential of the inside relative to the outside zero. In mathematical terms, the definition of voltage begins with the concept of an electric field E, a vector field assigning a magnitude and direction to each point in space. In many situations, the electric field is a conservative field, which means that it can be expressed as the gradient of a scalar function V, that is, E = –∇V.
This scalar field V is referred to as the voltage distribution. Note that the definition allows for an arbitrary constant of integration—this is why absolute values of voltage are not meaningful. In general, electric fields can be treated as
In neuroscience, the threshold potential is the critical level to which a membrane potential must be depolarized to initiate an action potential. Threshold potentials are necessary to regulate and propagate signaling in both the central nervous system and the peripheral nervous system. Most the threshold potential is a membrane potential value between –50 and –55 mV, but can vary based upon several factors. A neuron's resting membrane potential can be altered to either increase or decrease likelihood of reaching threshold via sodium and potassium ions. An influx of sodium into the cell through open, voltage-gated sodium channels can depolarize the membrane past threshold and thus excite it while an efflux of potassium or influx of chloride can hyperpolarize the cell and thus inhibit threshold from being reached. Initial experiments revolved around the concept that any electrical change, brought about in neurons must occur through the action of ions; the German physical chemist Walther Nernst applied this concept in experiments to discover nervous excitability, concluded that the local excitatory process through a semi-permeable membrane depends upon the ionic concentration.
Ion concentration was shown to be the limiting factor in excitation. If the proper concentration of ions was attained, excitation would occur; this was the basis for discovering the threshold value. Along with reconstructing the action potential in the 1950s, Alan Lloyd Hodgkin and Andrew Huxley were able to experimentally determine the mechanism behind the threshold for excitation, it is known as the Hodgkin–Huxley model. Through use of voltage clamp techniques on a squid giant axon, they discovered that excitable tissues exhibit the phenomenon that a certain membrane potential must be reached in order to fire an action potential. Since the experiment yielded results through the observation of ionic conductance changes and Huxley used these terms to discuss the threshold potential, they suggested that there must be a discontinuity in the conductance of either sodium or potassium, but in reality both conductances tended to vary smoothly along with the membrane potential. They soon discovered that at threshold potential, the inward and outward currents, of sodium and potassium ions were equal and opposite.
As opposed to the resting membrane potential, the threshold potential's conditions exhibited a balance of currents that were unstable. Instability refers to the fact that any further depolarization activates more voltage-gated sodium channels, the incoming sodium depolarizing current overcomes the delayed outward current of potassium. At resting level, on the other hand, the potassium and sodium currents are equal and opposite in a stable manner, where a sudden, continuous flow of ions should not result; the basis is that at a certain level of depolarization, when the currents are equal and opposite in an unstable manner, any further entry of positive charge generates an action potential. This specific value of depolarization is otherwise known as the threshold potential; the threshold value controls whether or not the incoming stimuli are sufficient to generate an action potential. It relies on a balance of incoming excitatory stimuli; the potentials generated by the stimuli are additive, they may reach threshold depending on their frequency and amplitude.
Normal functioning of the central nervous system entails a summation of synaptic inputs made onto a neuron's dendritic tree. These local graded potentials, which are associated with external stimuli, reach the axon initial segment and build until they manage to reach the threshold value; the larger the stimulus, the greater the depolarization, or attempt to reach threshold. The task of depolarization requires several key steps; the ion conductances involved depend on the membrane potential and the time after the membrane potential changes. The phospholipid bilayer of the cell membrane is, in itself impermeable to ions; the complete structure of the cell membrane includes many proteins that are embedded in or cross the lipid bilayer. Some of those proteins allow for the specific passage of ions, ion channels. Leak potassium channels allow potassium to flow through the membrane in response to the disparity in concentrations of potassium inside and outside the cell; the loss of positive charges of the potassium ions from the inside of the cell results in a negative potential there compared to the extracellular surface of the membrane.
A much smaller "leak" of sodium into the cell results in the actual resting potential, about –70 mV, being less negative than the calculated potential for K+ alone, the equilibrium potential, about –90 mV. The sodium-potassium ATPase is an active transporter within the membrane that pumps potassium back into the cell and sodium out of the cell, maintaining the concentrations of both ions as well as preserving the voltage polarization. However, once a stimulus activates the voltage-gated sodium channels to open, positive sodium ions flood into the cell and the voltage increases; this process can be initiated by ligand or neurotransmitter binding to a ligand-gated channel. More sodium is outside the cell relative to the inside, the positive charge within the cell propels the outflow of potassium ions through delayed-rectifier voltage-gated potassium channels. Since the potassium channels within the cell membrane are delayed, any further entrance of sodium activates more and more voltage-gated sodium channels.
Depolarization above threshold results in an increase in the conductance of Na sufficient for inward sodium movement to swamp outwar
A nerve is an enclosed, cable-like bundle of nerve fibres called axons, in the peripheral nervous system. A nerve provides a common pathway for the electrochemical nerve impulses called action potentials that are transmitted along each of the axons to peripheral organs or, in the case of sensory nerves, from the periphery back to the central nervous system; each axon within the nerve is an extension of an individual neuron, along with other supportive cells such as Schwann cells that coat the axons in myelin. Within a nerve, each axon is surrounded by a layer of connective tissue called the endoneurium; the axons are bundled together into groups called fascicles, each fascicle is wrapped in a layer of connective tissue called the perineurium. The entire nerve is wrapped in a layer of connective tissue called the epineurium. In the central nervous system, the analogous structures are known as tracts; each nerve is covered on the outside by a dense sheath of the epineurium. Beneath this is a layer of flat cells, the perineurium, which forms a complete sleeve around a bundle of axons.
Perineurial septae subdivide it into several bundles of fibres. Surrounding each such fibre is the endoneurium; this forms an unbroken tube from the surface of the spinal cord to the level where the axon synapses with its muscle fibres, or ends in sensory receptors. The endoneurium consists of an inner sleeve of material called the glycocalyx and an outer, meshwork of collagen fibres. Nerves are bundled and travel along with blood vessels, since the neurons of a nerve have high energy requirements. Within the endoneurium, the individual nerve fibres are surrounded by a low-protein liquid called endoneurial fluid; this acts in a similar way to the cerebrospinal fluid in the central nervous system and constitutes a blood-nerve barrier similar to the blood-brain barrier. Molecules are thereby prevented from crossing the blood into the endoneurial fluid. During the development of nerve edema from nerve irritation, the amount of endoneurial fluid may increase at the site of irritation; this increase in fluid can be visualized using magnetic resonance neurography, thus MR neurography can identify nerve irritation and/or injury.
Nerves are categorized into three groups based on the direction that signals are conducted: Afferent nerves conduct signals from sensory neurons to the central nervous system, for example from the mechanoreceptors in skin. Efferent nerves conduct signals from the central nervous system along motor neurons to their target muscles and glands. Mixed nerves contain both afferent and efferent axons, thus conduct both incoming sensory information and outgoing muscle commands in the same bundle. Nerves can be categorized into two groups based on where they connect to the central nervous system: Spinal nerves innervate much of the body, connect through the vertebral column to the spinal cord and thus to the central nervous system, they are given letter-number designations according to the vertebra through which they connect to the spinal column. Cranial nerves innervate parts of the head, connect directly to the brain, they are assigned Roman numerals from 1 to 12, although cranial nerve zero is sometimes included.
In addition, cranial nerves have descriptive names. Specific terms are used to describe their actions. A nerve that supplies information to the brain from an area of the body, or controls an action of the body is said to "innervate" that section of the body or organ. Other terms relate to whether the nerve affects the same side or opposite side of the body, to the part of the brain that supplies it. Nerve growth ends in adolescence, but can be re-stimulated with a molecular mechanism known as "Notch signaling". If the axons of a neuron are damaged, as long as the cell body of the neuron is not damaged, the axons would regenerate and remake the synaptic connections with neurons with the help of guidepost cells; this is referred to as neuroregeneration. The nerve begins the process by destroying the nerve distal to the site of injury allowing Schwann cells, basal lamina, the neurilemma near the injury to begin producing a regeneration tube. Nerve growth factors are produced causing many nerve sprouts to bud.
When one of the growth processes finds the regeneration tube, it begins to grow towards its original destination guided the entire time by the regeneration tube. Nerve regeneration is slow and can take up to several months to complete. While this process does repair some nerves, there will still be some functional deficit as the repairs are not perfect. A nerve conveys information in the form of electrochemical impulses carried by the individual neurons that make up the nerve; these impulses are fast, with some myelinated neurons conducting at speeds up to 120 m/s. The impulses travel from one neuron to another by crossing a synapse, the message is converted from electrical to chemical and back to electrical. Nerves can be categorized into two groups based on function: An afferent nerve fiber conducts sensory information from a sensory neuron to the central nervous system, where the information is processed. Bundles of fibres or axons, in the peripheral nervous system are called nerves, bundles of afferent fibers are known as sensory nerves.
An efferent nerve fiber conducts signals from a motor neuron in the central nervous system to muscles. Bundles of these fibres are known as efferent nerves; the nervous system is the part of an animal that coordinates its actions by transmitting signals to and from different parts of its body. In vertebrates it consists of two main par
The soma, neurocyton, or cell body is the bulbous, non-process portion of a neuron or other brain cell type, containing the cell nucleus. The word'soma' comes from the Greek'σῶμα', meaning'body'. Although it is used to refer to neurons, it can refer to other cell types as well, including astrocytes and microglia. There are many different specialized types of neurons, their sizes vary from as small as about 5 micrometres to over 10 millimetre for some of the smallest and largest neurons of invertebrates, respectively; the soma of a neuron contains many organelles, including granules called Nissl granules, which are composed of rough endoplasmic reticulum and free polyribosomes. The cell nucleus is a key feature of the soma; the nucleus is the source of most of the RNA, produced in neurons. In general, most proteins are produced from mRNAs; this creates a challenge for supplying new proteins to axon endings that can be a meter or more away from the soma. Axons contain microtubule-associated motor proteins that transport protein-containing vesicles between the soma and the synapses at the axon terminals.
Such transport of molecules away from the soma maintains critical cell functions. The axon hillock is a specialized domain of the neuronal cell body. A high amount of protein synthesis occurs in this region, as it contains a large number of Nissl granules and polyribosomes. Within the axon hillock, materials are sorted as either items that will enter the axon or will remain in the soma. In addition, the axon hillock has a specialized plasma membrane that contains large numbers of voltage-gated ion channels, since this is most the site of action potential initiation; the survival of some sensory neurons depends on axon terminals making contact with sources of survival factors that prevent apoptosis. The survival factors are neurotrophic factors, including molecules such as nerve growth factor. NGF interacts with receptors at axon terminals, this produces a signal that must be transported up the length of the axon to the nucleus. A current theory of how such survival signals are sent from axon endings to the soma includes the idea that NGF receptors are endocytosed from the surface of axon tips and that such endocytotic vesicles are transported up the axon.
Histology image: 3_09 at the University of Oklahoma Health Sciences Center - "Slide 3 Spinal cord"
Neurotransmitters are endogenous chemicals that enable neurotransmission. It is a type of chemical messenger which transmits signals across a chemical synapse, such as a neuromuscular junction, from one neuron to another "target" neuron, muscle cell, or gland cell. Neurotransmitters are released from synaptic vesicles in synapses into the synaptic cleft, where they are received by neurotransmitter receptors on the target cells. Many neurotransmitters are synthesized from simple and plentiful precursors such as amino acids, which are available from the diet and only require a small number of biosynthetic steps for conversion. Neurotransmitters play a major role in shaping everyday life and functions, their exact numbers are unknown, but more than 200 chemical messengers have been uniquely identified. Neurotransmitters are stored in synaptic vesicles, clustered close to the cell membrane at the axon terminal of the presynaptic neuron. Neurotransmitters are released into and diffuse across the synaptic cleft, where they bind to specific receptors on the membrane of the postsynaptic neuron.
Most neurotransmitters are about the size of a single amino acid. A released neurotransmitter is available in the synaptic cleft for a short time before it is metabolized by enzymes, pulled back into the presynaptic neuron through reuptake, or bound to a postsynaptic receptor. Short-term exposure of the receptor to a neurotransmitter is sufficient for causing a postsynaptic response by way of synaptic transmission. In response to a threshold action potential or graded electrical potential, a neurotransmitter is released at the presynaptic terminal. Low level "baseline" release occurs without electrical stimulation; the released neurotransmitter may move across the synapse to be detected by and bind with receptors in the postsynaptic neuron. Binding of neurotransmitters may influence the postsynaptic neuron in either an inhibitory or excitatory way; this neuron may be connected to many more neurons, if the total of excitatory influences are greater than those of inhibitory influences, the neuron will "fire".
It will create a new action potential at its axon hillock to release neurotransmitters and pass on the information to yet another neighboring neuron. Until the early 20th century, scientists assumed that the majority of synaptic communication in the brain was electrical. However, through the careful histological examinations by Ramón y Cajal, a 20 to 40 nm gap between neurons, known today as the synaptic cleft, was discovered; the presence of such a gap suggested communication via chemical messengers traversing the synaptic cleft, in 1921 German pharmacologist Otto Loewi confirmed that neurons can communicate by releasing chemicals. Through a series of experiments involving the vagus nerves of frogs, Loewi was able to manually slow the heart rate of frogs by controlling the amount of saline solution present around the vagus nerve. Upon completion of this experiment, Loewi asserted that sympathetic regulation of cardiac function can be mediated through changes in chemical concentrations. Furthermore, Otto Loewi is credited with discovering acetylcholine —the first known neurotransmitter.
Some neurons do, communicate via electrical synapses through the use of gap junctions, which allow specific ions to pass directly from one cell to another. There are four main criteria for identifying neurotransmitters: The chemical must be synthesized in the neuron or otherwise be present in it; when the neuron is active, the chemical must produce a response in some target. The same response must be obtained. A mechanism must exist for removing the chemical from its site of activation. However, given advances in pharmacology and chemical neuroanatomy, the term "neurotransmitter" can be applied to chemicals that: Carry messages between neurons via influence on the postsynaptic membrane. Have little or no effect on membrane voltage, but have a common carrying function such as changing the structure of the synapse. Communicate by sending reverse-direction messages that affect the release or reuptake of transmitters; the anatomical localization of neurotransmitters is determined using immunocytochemical techniques, which identify the location of either the transmitter substances themselves, or of the enzymes that are involved in their synthesis.
Immunocytochemical techniques have revealed that many transmitters the neuropeptides, are co-localized, that is, one neuron may release more than one transmitter from its synaptic terminal. Various techniques and experiments such as staining and collecting can be used to identify neurotransmitters throughout the central nervous system. There are many different ways. Dividing them into amino acids and monoamines is sufficient for some classification purposes. Major neurotransmitters: Amino acids: glutamate, aspartate, D-serine, γ-aminobutyric acid, glycine Gasotransmitters: nitric oxide, carbon monoxide, hydrogen sulfide Monoamines: dopamine, epinephrine, serotonin Trace amines: phenethylamine, N-methylphenethylamine, tyramine, 3-iodothyronamine, tryptamine, etc. Peptides: oxytocin, substance P, cocaine and amphetamine regulated transcript, opioid peptides Purines: adenosine triphosphate, adenosine Catecholamines: dopamine, epinephrine Others: acetylcholine, etc. In addition, over 50 neuroactive pepti
Signal transduction is the process by which a chemical or physical signal is transmitted through a cell as a series of molecular events, most protein phosphorylation catalyzed by protein kinases, which results in a cellular response. Proteins responsible for detecting stimuli are termed receptors, although in some cases the term sensor is used; the changes elicited by ligand binding in a receptor give rise to a biochemical cascade, a chain of biochemical events as a signaling pathway. When signaling pathways interact with one another they form networks, which allow cellular responses to be coordinated by combinatorial signaling events. At the molecular level, such responses include changes in the transcription or translation of genes, post-translational and conformational changes in proteins, as well as changes in their location; these molecular events are the basic mechanisms controlling cell growth, proliferation and many other processes. In multicellular organisms, signal transduction pathways have evolved to regulate cell communication in a wide variety of ways.
Each component of a signaling pathway is classified according to the role it plays with respect to the initial stimulus. Ligands are termed first messengers, while receptors are the signal transducers, which activate primary effectors; such effectors are linked to second messengers, which can activate secondary effectors, so on. Depending on the efficiency of the nodes, a signal can be amplified, so that one signaling molecule can generate a response involving hundreds to millions of molecules; as with other signals, the transduction of biological signals is characterised by delay, signal feedback and feedforward and interference, which can range from negligible to pathological. With the advent of computational biology, the analysis of signaling pathways and networks has become an essential tool to understand cellular functions and disease, including signaling rewiring mechanisms underlying responses to acquired drug resistance; the basis for signal transduction is the transformation of a certain stimulus into a biochemical signal.
The nature of such stimuli can vary ranging from extracellular cues, such as the presence of EGF, to intracellular events, such as the DNA damage resulting from replicative telomere attrition. Traditionally, signals that reach the central nervous system are classified as senses; these are transmitted from neuron to neuron in a process called synaptic transmission. Many other intercellular signal relay mechanisms exist in multicellular organisms, such as those that govern embryonic development; the majority of signal transduction pathways involve the binding of signaling molecules, known as ligands, to receptors that trigger events inside the cell. The binding of a signaling molecule with a receptor causes a change in the conformation of the receptor, known as receptor activation. Most ligands are soluble molecules from the extracellular medium which bind to cell surface receptors; these include growth factors and neurotransmitters. Components of the extracellular matrix such as fibronectin and hyaluronan can bind to such receptors.
In addition, some molecules such as steroid hormones are lipid-soluble and thus cross the plasma membrane to reach nuclear receptors. In the case of steroid hormone receptors, their stimulation leads to binding to the promoter region of steroid-responsive genes. Not all classifications of signaling molecules take into account the molecular nature of each class member. For example, odorants belong to a wide range of molecular classes, as do neurotransmitters, which range in size from small molecules such as dopamine to neuropeptides such as endorphins. Moreover, some molecules may fit into more than one class, e.g. epinephrine is a neurotransmitter when secreted by the central nervous system and a hormone when secreted by the adrenal medulla. Some receptors such as HER2 are capable of ligand-independent activation when overexpressed or mutated; this leads to constituitive activation of the pathway, which may or may not be overturned by compensation mechanisms. In the case of HER2, which acts as a dimerization partner of other EGFRs, constituitive activation leads to hyperproliferation and cancer.
The prevalence of basement membranes in the tissues of Eumetazoans means that most cell types require attachment to survive. This requirement has led to the development of complex mechanotransduction pathways, allowing cells to sense the stiffness of the substratum; such signaling is orchestrated in focal adhesions, regions where the integrin-bound actin cytoskeleton detects changes and transmits them downstream through YAP1. Calcium-dependent cell adhesion molecules such as cadherins and selectins can mediate mechanotransduction. Specialised forms of mechanotransduction within the nervous system are responsible for mechanosensation: hearing, touch and balance. Cellular and systemic control of osmotic pressure is critical for homeostasis. There are three ways in which cells can detect osmotic stimuli: as changes in macromolecular crowding, ionic strength, changes in the properties of the plasma membrane or cytoskeleton; these changes are detected by proteins known as osmoreceptors. In humans, the best characterised osmosensors are transient receptor potential channels present in the primary cilium of human cells.
In yeast, the HOG pathway has been extensively characterised. The sensing of temperature in cells is known as thermoception and is mediated by transient receptor potential channels. Addi