Neurotransmitter Receptors in Cell Signaling Transduction

Neurotransmitter Receptor list in Cell Signaling Transduction

Neurotransmitter Receptors in Cell Signaling Transduction: Information

Chemical transmission is the major means by which nerves communicate with one another in the nervous system. Many different types of neurotransmitters play an important role in the process of chemical transdmittion. The neurotransmitters achieve cell signaling transduction through neurotransmitter receptors on the postsynaptic membrane. The neurotransmitter receptor perform large specificity and potency. Many receptors have been isolated and purified biochemically, and many have also been cloned and sequenced. Neurotransmitter receptors can also be grouped according to the type of primary effector to which they couple. This classification leads to four major categories of receptors.

Four groups of Neurotransmitter Receptor in cell signaling transduction

Group I: Ligand-gated ion channels as neurotransmitter receptors

These ligand-gated ion channels include nAChR, GluN1, GluN2A-D, GluN3A,B, GluA1-4, GluK1-3, 4-5, GABAA, GlyR, IP3-R1, IP3-R2, IP3-R3, 5HT3, P2X1-7 and Nicotinic cholinergic (muscle [αβγδε] and neuronal [α or αβ] subtypes).

Receptors in this category include those that are activated by synaptically released neurotransmitter and occur on the cell surface (mostly, the intracellular ligand-gated receptor for IP3 is present in the smooth endoplasmic reticulum). Upon the binding of an agonist to these ligand-gated ion channels, the receptors undergo a conformational change that facilitates opening of the intrinsic ion channel (some ligand gated ion channel receptors (e.g., NMDA and GABAA) are also found at extrasynaptic locations).

The permeability to specific ions is a characteristic of the receptor; for example, both the neuronal nicotinic cholinergic receptors (nAChR) and N-methyl D-aspartate (NMDA) receptors are selectively permeable to Na+ and Ca2+ ions, whereas GABAA and glycine receptors are primarily permeable to Cl- ions. As a result of the changes in ion conductance, the membrane potential may become either depolarized, as occurs for nAChRs or NMDA receptors, or hyperpolarized, as observed for GABAA or glycine receptors.

Group II: Receptors with intrinsic guanylyl cyclase activity as neurotransmitter receptors

The representative receptor with intrinsic guanylyl cyclase activity is GC-B.
Receptors in the this group possess intrinsic guanylyl cyclase activity and generate cyclic GMP (cGMP) upon activation of a receptor. These receptors consist of an extracellular binding domain, a single transmembrane-spanning domain (TMD), a protein kinase–like domain and a guanylyl cyclase catalytic domain.

Ligand binding results in a conformational change in the receptor and activation of the guanylyl cyclase catalytic region. Receptors with intrinsic guanylyl cyclase activity are often very highly phosphorylated in the absence of agonist and rapidly undergo dephosphorylation upon activation.

Group III: Receptors with intrinsic or associated tyrosine kinase activity as neurotransmitter receptors

Receptors with intrinsic or associated tyrosine kinase activity include TrkB, EGFR, FGFR1- FGFR4, IGFR-1, Trk A, ErbB2, ErbB3, ErbB4, Trk C, PDGFR α and β, gp130 + CNTFRα and LIFRβ, 2 x gp130 + IL6Rα and gp130 + LIFRβ.

Receptors in the third group possess intrinsic receptor tyrosine kinase (RTK) activity themselves or are closely associated with cytoplasmic tyrosine kinases (RATK). Structurally, RTKs possess an extracellular ligandbinding domain, a single TMD and an intracellular catalytic kinase domain.

Three distinct events underlie signal transduction at RTKs: (1) Initially, upon ligand binding to an RTK, the receptor undergoes a dimerization that results in the juxtaposition of the two cytoplasmic domains. (2) Contact between these domains is thought to result in a stimulation of catalytic activity, (3) which in turn results in an intermolecular autophosphorylation of tyrosine residues both within and outside of the kinase domain. Once autophosphorylated, RTKs can recruit a number of cytoplasmic proteins and initiate a series of reactions involving protein–protein interactions.

RATKs, such as those for the neurotrophic cytokines (leukemia inhibitory factor, interleukin-6 or ciliary neurotrophic factor) do not possess intrinsic tyrosine kinase activity themselves, but upon activation, they undergo dimerization and are then able to recruit cytoplasmic tyrosine kinases (such as Janus kinase). The latter then phosphorylate the RATK on tyrosine residues (in addition to being tyrosine phosphorylated themselves) and facilitate protein–protein interactions, as observed for RTKs.

Group IV: G-protein-coupled receptors as neurotransmitter receptors

G-protein-coupled receptors within neurotransmitter receptors include Acetylcholine receptors, Adenosine receptors, ATP receptors, Dopamine receptors…… This group of receptors involves G proteins. Numerically, more diverse types of receptors have been demonstrated to operate via an intervening G protein than by any other mechanism. These G protein–coupled receptors(GPCRs) have a characteristic seven TMD structure.

G-protein-coupled neurotransmitter receptors can be further divided into four functional categories: (1) Some GPCRs, such as GABAB, α2-adrenergic, D2-dopaminergic or M2 muscarinic (mAChR), regulate the changes in K+ conductance independently of second-messenger production. (2) A second group of GPCRs is linked to the modulation of adenylyl cyclase activity. This regulation may be either positive, as in the case of activation of the β2-adrenergic receptor, or negative, as occurs following activation of the α2-adrenergic receptor. Changes in the concentrations of cAMP regulate the activity of protein kinase A (PKA). (3) A third group of GPCRs is linked to the activation of phosphoinositide-specific phospholipase C (PLC) with the attendant breakdown of PIP2 and formation of IP3 and DAG. These receptors are linked to changes in Ca2+ homeostasis and protein phosphorylation via the action of protein kinase C (PKC). Other effector enzymes that may be regulated by IP3-linked GPCRs include phospholipases A2 and D. (3) A fourth, and unique, mechanism for the activation of a GPCR is that utilized by the visual pigment rhodopsin, which structurally is a prototypical GPCR. However, in this case it is light, rather than a chemical stimulus, that triggers the activation of rhodopsin. Photoactivated rhodopsin activates transducin, a G-protein, which is coupled to cGMP phosphodiesterase with a concomitant increased rate in the hydrolysis of cGMP to GMP.

Neurotransmitter Receptors in Cell Signaling Transduction: Reference

• Holz R W, Fisher S K. Synaptic transmission and cellular signaling: an overview[J]. Basic neurochemistry. Philadelphia: Lippincott Williams & Wilkins, 1999: 191-212.