THE 7-TRANSMEMBRANE RECEPTORS - PHYSIOLOGY AND PATHOLOGY OF TRANSDUCTION

The membrane-bound receptors can be classified into a small number of families and the largest family is composed of receptors coupled to G proteins (GPCR). This family contains several hundred members, able to recognize various messages (such as photons, ions, amino acids, etc.). These GPCR are monomeric proteins possessing a common topology, similar to that of rhodopsine, comprising 7 transmembrane domains (TD). They call be subclassified into three groups and have no homology in their primary sequence. The localization of the ligand binding domain lies within the TDs (rhodopsin, beta(2)-adrenergic receptor...) and more or less within the external N-terminal domain. GPCRs catalyse the GDP/GTP exchange on trimeric G proteins (alpha beta gamma). They control a network of transductions either via the alpha subunits of these G proteins or via the beta gamma dimers (in particular Ras protein activation). Activating or inactivating mutations of these GPCRs have been described to cause pathologies such as retinitis pigmentosa, thyroid adenoma, precocious puberty or diabetes insipidus or familial glucocorticoid deficiency. Apart from these mutations, polymorphism in the genes coding GPCRs, may be at the origin of individual differences, in particular in receptors controlling sensory perception and other functions of the nervous system.