cell signaling

Cells, whether unicellular organisms or cells within multicellular organisms, adjust to signals within their environment and communicate with other cells.

▼ autocrine : cellular responses : combinatorial : contact-dependent signaling : cytokines : delay/rapidity : distance of signal : endocrine : environmental signals : evolution : histidine kinase : hormones : neuronal signaling : neurotransmitters : paracrine : prokaryote signaling : rapidity/delay : receptor proteins : receptors : regulator proteins : SH domains : signal termination : signaling distance : signal transduction ▼

Receptors are molecules that receive signals by binding ligands, for which receptors have varying binding affinity. Signal transduction is the process of converting signals from one form to another, ultimately adjusting an intracellular process, as in metabolic regulation, or an intranuclear process, such as gene expression.

Signaling operates at various distances:
● contact signaling – particularly important in immune signaling and during development

signaling mediated by synthesized signal mediators
● autocrine – chemical mediators (cytokines, growth factors) that operate on the cell that produces the mediator [1, 2]

signaling mediated by secreted signal mediators
● paracrine – short-range
● endocrine – long-range via hormones

Neurons signal at long-range by virtue of their long axonal processes, but neurotransmitters released into the synaptic cleft operate at short-range, enabling rapid, precise signaling.

Speed of signaling is determined by:
● speed of production of the signal (synthesis of mediators)
● speed of delivery of signal mediators (delivery of mediators to target cells)
● speed of cellular response to the signal
● depolarization, impulse propagation, repolarization of nerve cells

Signals are terminated by:
● dissociation of mediator ligand from receptor
● absorption of mediator by neighboring target cells (neurotransmitters and other paracrine mediators)
● enzymatic destruction of mediators
● immobilization by adsorption of mediators in ECM or by binding to intracellular proteins

Signal transduction is usually performed by enzymes in association with second messengers. Signaling proteins operate in a combinatorial fashion within signaling networks, greatly extending the biological roles of individual proteins. The simplest such system comprises two components – a histidine kinase protein that receives a signal and transmits it, via phosphorelay, to a partner response-regulator protein. Protein domains and motif interactions display considerable flexibility, providing an obvious evolutionary advantage. For example, single amino acid substitutions alter the binding specificity of SH2 domains such that specificity can change quite rapidly, enabling formation of new signaling connections as metazoan organisms became more complex.

Environmental signals include mechanical stimuli (light, sound) and chemical stimuli. The origin of a biochemical stimulus may be the cell itself (autocrine), adjacent cells (paracrine), the plasma membrane of adjacent cells (contact inhibition), or distant cells (endocrine).

Neurotransmission incorporates interaction between neurotransmitters and specific receptor proteins. Cytokines mediate paracrine stimulation, and hormones mediate endocrine stimulation.

Cellular responses to signaling include:
● alterations in gene expression (transcription)
● alteration of electrophysiological charge
● cellular cycling and reproduction
● regulation of cellular metabolic processes
● biosynthesis with or without secretion
● cellular growth
● chemotaxis, migration, and, in multicellular organisms, extravasation
● initiation of immune and inflammatory responses
● differentiation into cell lines or maturation of cell lines
● cellular survival or apoptosis

Intracellular interactions in prokaryotes
Four kinds of cell interactions can be distinguished:
1) Transfer of a chemical signal from one cell to another. The variety of such transfers is presented in several examples.
2) Signaling by direct physical contact between two cell bodies, which may involve their surfaces or cell appendages, such as fibrils, pili, or flagella (bacterial flagella). Direct physical contact is often involved in cell swarming.
3) Syntrophic metabolism. Schink Syntrophism Among Prokaryotes.
4) Gene transfer from one cell to another.


• bacterial interactions • concentration gradients • ion channels • protein pumps • receptor proteins • receptor-mediated endocytosis • GPCRs • GPCR families • hormones • neurotransmission • Nitric Oxide • neuronal interconnections • phosphotransfer-mediated signaling pathways • Protein Kinase Signaling Networks • signaling gradients :

KEGG Encyclopedia : Pathway ABC transporters : Pathway Phosphotransferase system (PTS) : Pathway Two-component system : Pathway MAPK signaling pathway : Pathway Wnt signaling pathway : Pathway Notch signaling pathway : Pathway Hedgehog signaling pathway : Pathway TGF-beta signaling pathway : Pathway VEGF signaling pathway : Pathway Jak-STAT signaling pathway : Pathway Calcium signaling pathway : Pathway Phosphatidylinositol signaling system : Pathway mTOR signaling pathway : Pathway Neuroactive ligand-receptor interaction : Pathway Cytokine-cytokine receptor interaction : Pathway ECM-receptor interaction : Pathway Cell adhesion molecules (CAMs) : Orthology Transporters (+diseases) : Orthology Two-component system : Orthology Receptors and channels (+diseases) : Orthology Cytokines :
Orthology Cell adhesion molecules (CAMs) : Orthology CAM ligands : Orthology CD molecules :
Orthology GTP-binding proteins :

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neuronal interconnections

The neuron is the basic operating unit of the central nervous system. Inter-neuronal information processing, involving complex neural networks, provides the nervous system with its enormous functional capacity. The human brain contains about 10^(11) neurons*, which connect, via synapses, with an average of 1000 other neurons. In total, the human brain may contain somewhere between 10^(14) and 10^(15) synaptic connections. Neurotransmitter chemicals effect the connection between neurons, when they cross the gap between neurons and interact with specific receptor proteins. More than one hundred chemicals and a much larger number of receptors have been implicated in synaptic transmission. Some neurotransmitters are the targets of drug therapies. Receptor molecules are the targets of neurotoxic venomous substances.* 10^(11) is equivalent to a 10 followed by 11 zeros = 1,000,000,000,000

Depolarization of neuronal cell membranes beyond a necessary threshold results in action potentials which propagate along the soma/axon/dendrite to the pre-synaptic terminal bulb. At the pre-synaptic terminal, the wave of depolarization results in release of vesicle-stored neurotransmitters into the synaptic cleft. Released neurotransmitters bind to specific post-synaptic receptors that open ion channels, resulting in further depolarization and post-synaptic action potentials.

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neurotransmission

Roughly 10 small-molecule transmitters and over 50 recognized neuroactive peptides comprise the commonly recognized neurotransmitters, molecules involved in signalling between cells. A variety of macromolecules act as receptors for neurotransmitters and hormones (molecules that act at a distance from their production).

There exist numerous receptors for each neurotransmitter, so receptors play an important role in neurotransmission. Most neurotransmitter receptors belong to a class of proteins known as the serpentine receptors, or GPCRs, in which a characteristic trans-membrane structure spans the cell membrane seven times. Intracellular signalling is carried out by association of the neurotransmitter with G-proteins (small GTP-binding and hydrolyzing proteins), or with protein kinases, or by the receptor itself in the form of a ligand-gated ion channel (acetylcholine receptor). Neurotransmitter receptors are subject to ligand-induced desensitization whereby they become unresponsive upon prolonged exposure to their neurotransmitter. The NMDA receptor is a neural receptor that is expressed at excitatory glutamatergic synapses and is critical for normal brain function. At a cellular level, this receptor plays a pivotal role in triggering and controlling synaptic plasticity, and so is important for learning and memory.

Among the small-molecule neurotransmitters are: acetylcholine, 5 amines, and 3 or 4 amino acids. The purines adenosine, ATP, GTP, and their derivatives are also neurotransmitters. In addition to amines, amino acids, purines, and acetylcholine, fatty acids are candidates for neurotransmitter (endogenous canabinoid). The monoamine neurotransmitters include the catecholamines dopamine, epinephrine, and norepinephrine, which are derived from the amino acids phenylalanine and tyrosine. Serotonin, or 5-HT is a monoamine product of the amino acid tryptophan. The hydrophilic vasoactive amine histamine is derived from the amino acid histidine. Aspartate, glutamate, and GABA are also derived from amino acids (aspartic acid, glutamic acid). Glycine is the smallest amino acid, and acts as a neurotransmitter.

The catecholamine neurotransmitter dopamine is a precursor in the biosynthetic pathway to the other catecholamine neurotransmitters epinephrine (adrenaline) and norepinephrine (noradrenaline). Dopamine is synthesized in the body (predominantly in neurons and adrenals) by the decarboxylation of l-dopa by the enzyme aromatic-L-amino-acid decarboxylase. Dopamine beta hydroxylase converts dopamine to norepinephrine, and phenylethanoamine N-methyl transferase converts norepinephrine to epinephrine.

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