Hormones—or any molecule that binds to a receptor, known as a ligand—that are lipid-insoluble (water-soluble) are not able to diffuse across the cell membrane. In order to be able to affect a cell without entering it, these hormones bind to receptors on the cell membrane. When a first messenger, a hormone, binds to a receptor, a signal cascade is set off, causing second messengers, proteins inside the cell, to become activated, resulting in downstream effects.
Cell membrane receptors have three portions: an external ligand-binding domain, a transmembrane domain, and an internal domain. There are three categories of cell membrane receptors based on the consistency of the structure and function of these domains within each category.
One category is ligand-gated ion channels which, when bound to a ligand, undergo a conformational change, allowing ions through a channel formed by the transmembrane portion of the receptor.
A second category is G-proteins-coupled receptors which have a distinct structure with seven transmembrane domains. Binding of the external domain to a ligand causes the alpha subunit, one of three subunits attached to the internal portion of the receptor, to disassociate from the receptor and create a cellular response.
The third category of receptors, the enzyme-linked receptor—also called catalytic receptors—have an intracellular domain that is either associated with an enzyme or is an enzyme itself. When a ligand binds to the extracellular region, the intracellular enzyme becomes active, activating other proteins within the cell.
Cell membrane receptors are fundamental to cell function. Therefore, it is not surprising that many illnesses have been shown to be direct results of improperly functioning cell membrane receptors. For example, cholera develops when a G-protein-coupled receptor is disabled in the cells lining the small intestine.
The process of conversion of an extracellular stimulus to an intracellular response is known as signal transduction. This is a multi-step process involving a ligand binding to a receptor resulting in several molecular interactions within the cell. These interactions can get complicated because each step is dependent on multiple other reactions. This is a form of verification to make sure that proper cellular activities occur. This also often amplifies the response.
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