Cell surface receptor

Cell surface receptors (membrane receptors, transmembrane receptors) are

Many membrane receptors are transmembrane proteins. There are various kinds, including glycoproteins and lipoproteins.^[2] Hundreds of different receptors are known and many more have yet to be studied.^[3][4] Transmembrane receptors are typically classified based on their tertiary (three-dimensional) structure. If the three-dimensional structure is unknown, they can be classified based on membrane topology. In the simplest receptors, polypeptide chains cross the lipid bilayer once, while others, such as the G-protein coupled receptors, cross as many as seven times. Each cell membrane can have several kinds of membrane receptors, with varying surface distributions. A single receptor may also be differently distributed at different membrane positions, depending on the sort of membrane and cellular function. Receptors are often clustered on the membrane surface, rather than evenly distributed.^[5][6]

Two models have been proposed to explain transmembrane receptors' mechanism of action.

• Dimerization: The dimerization model suggests that prior to ligand binding, receptors exist in a
  monomeric form. When agonist binding occurs, the monomers combine to form an active dimer
  .
• Rotation: Ligand binding to the extracellular part of the receptor induces a rotation (conformational change) of part of the receptor's transmembrane helices. The rotation alters which parts of the receptor are exposed on the intracellular side of the membrane, altering how the receptor can interact with other proteins within the cell.[7]

The intracellular (or cytoplasmic) domain of the receptor interacts with the interior of the cell or organelle, relaying the signal. There are two fundamental paths for this interaction:^{[citation needed]}

• The intracellular domain communicates via protein-protein interactions against effector proteins, which in turn pass a signal to the destination.
• With enzyme-linked receptors, the intracellular domain has enzymatic activity. Often, this is tyrosine kinase activity. The enzymatic activity can also be due to an enzyme associated with the intracellular domain.

Signal transduction processes through membrane receptors involve the external reactions, in which the ligand binds to a membrane receptor, and the internal reactions, in which intracellular response is triggered.^[10][11]

Signal transduction through membrane receptors requires four parts:

• Extracellular signaling molecule: an extracellular signaling molecule is produced by one cell and is at least capable of traveling to neighboring cells.^{[citation needed]}
• Receptor protein: cells must have cell surface receptor proteins which bind to the signaling molecule and communicate inward into the cell.^{[citation needed]}
• Intracellular signaling proteins: these pass the signal to the organelles of the cell. Binding of the signal molecule to the receptor protein will activate intracellular signaling proteins that initiate a signaling cascade.^{[citation needed]}
• Target proteins: the conformations or other properties of the target proteins are altered when a signaling pathway is active and changes the behavior of the cell.^[11]

Membrane receptors are mainly divided by structure and function into 3 classes: The

• Ion channel linked receptors have ion channels for anions and cations, and constitute a large family of multipass transmembrane proteins. They participate in rapid signaling events usually found in electrically active cells such as
  neurotransmitters.^{[citation needed}
  ]
• Enzyme-linked receptors are either enzymes themselves, or directly activate associated enzymes. These are typically single-pass transmembrane receptors, with the enzymatic component of the receptor kept intracellular. The majority of enzyme-linked receptors are, or associate with, protein kinases.^[citation needed]
• G protein-coupled receptors are integral membrane proteins that possess seven transmembrane helices. These receptors activate a G protein upon agonist binding, and the G-protein mediates receptor effects on intracellular signaling pathways.^{[citation needed]}

During the signal transduction event in a neuron, the neurotransmitter binds to the receptor and alters the conformation of the protein. This opens the ion channel, allowing extracellular ions into the cell. Ion permeability of the plasma membrane is altered, and this transforms the extracellular chemical signal into an intracellular electric signal which alters the

The acetylcholine receptor is a receptor linked to a cation channel. The protein consists of four subunits: alpha (α), beta (β), gamma (γ), and delta (δ) subunits. There are two α subunits, with one acetylcholine binding site each. This receptor can exist in three conformations. The closed and unoccupied state is the native protein conformation. As two molecules of acetylcholine both bind to the binding sites on α subunits, the conformation of the receptor is altered and the gate is opened, allowing for the entry of many ions and small molecules. However, this open and occupied state only lasts for a minor duration and then the gate is closed, becoming the closed and occupied state. The two molecules of acetylcholine will soon dissociate from the receptor, returning it to the native closed and unoccupied state.^[13][14]

As of 2009, there are 6 known types of

G protein-coupled receptors comprise a large protein family of transmembrane receptors. They are found only in eukaryotes.^[15] The ligands which bind and activate these receptors include: photosensitive compounds, odors, pheromones, hormones, and neurotransmitters. These vary in size from small molecules to peptides and large proteins. G protein-coupled receptors are involved in many diseases, and thus are the targets of many modern medicinal drugs.^[16]

There are two principal signal transduction pathways involving the G-protein coupled receptors: the cAMP signaling pathway and the phosphatidylinositol signaling pathway.^[17] Both are mediated via G protein activation. The G-protein is a trimeric protein, with three subunits designated as α, β, and γ. In response to receptor activation, the α subunit releases bound guanosine diphosphate (GDP), which is displaced by guanosine triphosphate (GTP), thus activating the α subunit, which then dissociates from the β and γ subunits. The activated α subunit can further affect intracellular signaling proteins or target functional proteins directly.^{[citation needed]}

If the membrane receptors are denatured or deficient, the signal transduction can be hindered and cause diseases. Some diseases are caused by disorders of membrane receptor function. This is due to deficiency or degradation of the receptor via changes in the genes that encode and regulate the receptor protein. The membrane receptor

Through methods such as

• Adrenergic receptor
• Olfactory receptors
• Receptor tyrosine kinases
• Epidermal growth factor receptor
• Insulin Receptor
• Fibroblast growth factor receptors,
• High affinity neurotrophin receptors
• Ephrin receptors
• Integrins
• Low Affinity Nerve Growth Factor Receptor
• NMDA receptor
• Several
  Immune receptors
  • Toll-like receptor
  • T cell receptor
  • CD28
  • SCIMP protein

• Neuromodulators
• Second messenger
• Signalling lymphocyte activation molecule family