cell signaling cell signaling in biology, cell signaling (cell signalling in british english) or cell communication is the ability of a cell to receive, process, and transmit signals with its environment and with itself. cell signaling is a fundamental property of all cellular life in prokaryotes and eukaryotes. signals that originate from outside a cell (or extracellular signals) can be physical agents like mechanical pressure, voltage, temperature, light, or chemical signals (e.g., small molecules, peptides, or gas). cell signaling can occur over short or long distances, and as a result can be classified as autocrine, juxtacrine, intracrine, paracrine, or endocrine. signaling molecules can be synthesized from various biosynthetic pathways and released through passive or active transports, or even from cell damage. receptors play a key role in cell signaling as they are able to detect chemical signals or physical stimuli. receptors are generally proteins located on the cell surface or within the interior of the cell such as the cytoplasm, organelles, and nucleus. cell surface receptors usually bind with extracellular signals (or ligands), which causes a conformational change in the receptor that leads it to initiate enzymic activity, or to open or close ion channel activity. some receptors do not contain enzymatic or channel-like domains but are instead linked to enzymes or transporters. other receptors like nuclear receptors have a different mechanism such as changing their dna binding properties and cellular localization to the nucleus. signal transduction begins with the transformation (or transduction) of a signal into a chemical one, which can directly activate an ion channel (ligand-gated ion channel) or initiate a second messenger system cascade that propagates the signal through the cell. second messenger systems can amplify a signal, in which activation of a few receptors results in multiple secondary messengers being activated, thereby amplifying the initial signal (the first messenger). the downstream effects of these signaling pathways may include additional enzymatic activities such as proteolytic cleavage, phosphorylation, methylation, and ubiquitinylation. each cell is programmed to respond to specific extracellular signal molecules, and is the basis of development, tissue repair, immunity, and homeostasis. errors in signaling interactions may cause diseases such as cancer, autoimmunity, and diabetes. taxonomic range in many small organisms such as bacteria, quorum sensing enables individuals to begin an activity only when the population is sufficiently large. this signaling between cells was first observed in the marine bacterium aliivibrio fischeri, which produces light when the population is dense enough. the mechanism involves the production and detection of a signaling molecule, and the regulation of gene transcription in response. quorum sensing operates in both gram-positive and gram-negative bacteria, and both within and between species. in slime moulds, individual cells aggregate together to form fruiting bodies and eventually spores, under the influence of a chemical signal, known as an acrasin. the individuals move by chemotaxis, i.e. they are attracted by the chemical gradient. some species use cyclic amp as the signal; others such as polysphondylium violaceum use a dipeptide known as glorin. in plants and animals, signaling between cells occurs either through release into the extracellular space, divided in paracrine signaling (over short distances) and endocrine signaling (over long distances), or by direct contact, known as juxtacrine signaling such as notch signaling. autocrine signaling is a special case of paracrine signaling where the secreting cell has the ability to respond to the secreted signaling molecule. synaptic signaling is a special case of paracrine signaling (for chemical synapses) or juxtacrine signaling (for electrical synapses) between neurons and target cells. extracellular signal synthesis and release different types of extracellular signaling many cell signals are carried by molecules that are released by one cell and move to make contact with another cell. signaling molecules can belong to several chemical classes: lipids, phospholipids, amino acids, monoamines, proteins, glycoproteins, or gases. signaling molecules binding surface receptors are generally large and hydrophilic (e.g. trh, vasopressin, acetylcholine), while those entering the cell are generally small and hydrophobic (e.g. glucocorticoids, thyroid hormones, cholecalciferol, retinoic acid), but important exceptions to both are numerous, and the same molecule can act both via surface receptors or in an intracrine manner to different effects. in animal cells, specialized cells release these hormones and send them through the circulatory system to other parts of the body. they then reach target cells, which can recognize and respond to the hormones and produce a result. this is also known as endocrine signaling. plant growth regulators, or plant hormones, move through cells or by diffusing through the air as a gas to reach their targets. hydrogen sulfide is produced in small amounts by some cells of the human body and has a number of biological signaling functions. only two other such gases are currently known to act as signaling molecules in the human body: nitric oxide and carbon monoxide. exocytosis exocytosis is the process by which a cell transports molecules such as neurotransmitters and proteins out of the cell. as an active transport mechanism, exocytosis requires the use of energy to transport material. exocytosis and its counterpart, endocytosis, the process that brings substances into the cell, are used by all cells because most chemical substances important to them are large polar molecules that cannot pass through the hydrophobic portion of the cell membrane by passive transport. exocytosis is the process by which a large amount of molecules are released; thus it is a form of bulk transport. exocytosis occurs via secretory portals at the cell plasma membrane called porosomes. porosomes are permanent cup-shaped lipoprotein structures at the cell plasma membrane, where secretory vesicles transiently dock and fuse to release intra-vesicular contents from the cell. in exocytosis, membrane-bound secretory vesicles are carried to the cell membrane, where they dock and fuse at porosomes and their contents (i.e., water-soluble molecules) are secreted into the extracellular environment. this secretion is possible because the vesicle transiently fuses with the plasma membrane. in the context of neurotransmission, neurotransmitters are typically released from synaptic vesicles into the synaptic cleft via exocytosis; however, neurotransmitters can also be released via reverse transport through membrane transport proteins. autocrine differences between autocrine and paracrine signaling autocrine signaling involves a cell secreting a hormone or chemical messenger (called the autocrine agent) that binds to autocrine receptors on that same cell, leading to changes in the cell itself. this can be contrasted with paracrine signaling, intracrine signaling, or classical endocrine signaling. paracrine in paracrine signaling, a cell produces a signal to induce changes in nearby cells, altering the behaviour of those cells. signaling molecules known as paracrine factors diffuse over a relatively short distance (local action), as opposed to cell signaling by endocrine factors, hormones which travel considerably longer distances via the circulatory system; juxtacrine interactions; and autocrine signaling. cells that produce paracrine factors secrete them into the immediate extracellular environment. factors then travel to nearby cells in which the gradient of factor received determines the outcome. however, the exact distance that paracrine factors can travel is not certain. paracrine signals such as retinoic acid target only cells in the vicinity of the emitting cell. neurotransmitters represent another example of a paracrine signal. some signaling molecules can function as both a hormone and a neurotransmitter. for example, epinephrine and norepinephrine can function as hormones when released from the adrenal gland and are transported to the heart by way of the blood stream. norepinephrine can also be produced by neurons to function as a neurotransmitter within the brain. estrogen can be released by the ovary and function as a hormone or act locally via paracrine or autocrine signaling. although paracrine signaling elicits a diverse array of responses in the induced cells, most paracrine factors utilize a relatively streamlined set of receptors and pathways. in fact, different organs in the body - even between different species - are known to utilize a similar sets of paracrine factors in differential development. the highly conserved receptors and pathways can be organized into four major families based on similar structures: fibroblast growth factor (fgf) family, hedgehog family, wnt family, and tgf-β superfamily. binding of a paracrine factor to its respective receptor initiates signal transduction cascades, eliciting different responses. endocrine endocrine signals are called hormones. hormones are produced by endocrine cells and they travel through the blood to reach all parts of the body. specificity of signaling can be controlled if only some cells can respond to a particular hormone. endocrine signaling involves the release of hormones by internal glands of an organism directly into the circulatory system, regulating distant target organs. in vertebrates, the hypothalamus is the neural control center for all endocrine systems. in humans, the major endocrine glands are the thyroid gland and the adrenal glands. the study of the endocrine system and its disorders is known as endocrinology. juxtacrine juxtacrine signaling is a type of cell–cell or cell–extracellular matrix signaling in multicellular organisms that requires close contact. there are three types: a membrane ligand (protein, oligosaccharide, lipid) and a membrane protein of two adjacent cells interact. a communicating junction links the intracellular compartments of two adjacent cells, allowing transit of relatively small molecules. an extracellular matrix glycoprotein and a membrane protein interact. additionally, in unicellular organisms such as bacteria, juxtacrine signaling means interactions by membrane contact. juxtacrine signaling has been observed for some growth factors, cytokine and chemokine cellular signals, playing an important role in the immune response. juxtacrine signalling via direct membrane contacts is also present between neuronal cell bodies and motile processes of microglia both during development, and in the adult brain. receptors main article: receptor (biochemistry) transmembrane receptor working principle cells receive information from their neighbors through a class of proteins known as receptors. receptors may bind with some molecules (ligands) or may interact with physical agents like light, mechanical temperature, pressure, etc. reception occurs when the target cell (any cell with a receptor protein specific to the signal molecule) detects a signal, usually in the form of a small, water-soluble molecule, via binding to a receptor protein on the cell surface, or once inside the cell, the signaling molecule can bind to intracellular receptors, other elements, or stimulate enzyme activity (e.g. gasses), as in intracrine signaling. signaling molecules interact with a target cell as a ligand to cell surface receptors, and/or by entering into the cell through its membrane or endocytosis for intracrine signaling. this generally results in the activation of second messengers, leading to various physiological effects. in many mammals, early embryo cells exchange signals with cells of the uterus. in the human gastrointestinal tract, bacteria exchange signals with each other and with human epithelial and immune system cells. for the yeast saccharomyces cerevisiae during mating, some cells send a peptide signal (mating factor pheromones) into their environment. the mating factor peptide may bind to a cell surface receptor on other yeast cells and induce them to prepare for mating. cell surface receptors cell surface receptors play an essential role in the biological systems of single- and multi-cellular organisms and malfunction or damage to these proteins is associated with cancer, heart disease, and asthma. these trans-membrane receptors are able to transmit information from outside the cell to the inside because they change conformation when a specific ligand binds to it. there are three major types: ion channel linked receptors, g protein–coupled receptors, and enzyme-linked receptors. ion channel linked receptors the ampa receptor bound to a glutamate antagonist showing the amino terminal, ligand binding, and transmembrane domain, pdb 3kg2 ion channel linked receptors are a group of transmembrane ion-channel proteins which open to allow ions such as na+, k+, ca2+, and/or cl− to pass through the membrane in response to the binding of a chemical messenger (i.e. a ligand), such as a neurotransmitter. when a presynaptic neuron is excited, it releases a neurotransmitter from vesicles into the synaptic cleft. the neurotransmitter then binds to receptors located on the postsynaptic neuron. if these receptors are ligand-gated ion channels, a resulting conformational change opens the ion channels, which leads to a flow of ions across the cell membrane. this, in turn, results in either a depolarization, for an excitatory receptor response, or a hyperpolarization, for an inhibitory response. these receptor proteins are typically composed of at least two different domains: a transmembrane domain which includes the ion pore, and an extracellular domain which includes the ligand binding location (an allosteric binding site). this