Biodiversity of the genus Conus (Fleming, 1822): A rich source of bioactive peptides

In this paper, we present an overview of the biodiversity of both marine sn ails of the large genus Conus and their venoms. After a brief survey of Con idae malacology, we focus on the high degree of biodiversity of this genus, its specific biogeography as well as its habitat, and the relatively stric t diet of its members. The venom of Conidae species contains a large number of peptides that can interact selectively with key elements of the periphe ral and central nervous systems of vertebrates and invertebrates. Emphasis is on summarizing our current knowledge of the specific actions of venom co mponents on ionic channels, receptors and other key elements of cellular co mmunication. The peptides isolated from venoms, called conotoxins, form dif ferent families according to both their primary structure and their specifi c pharmacological targets. Three families encompassing the mu-, mu O- and d elta-conotoxins target voltage-sensitive sodium channels but with different modes of action or tissue selectivity. Another important class of conotoxi ns is the omega-conotoxin family which acts on voltage-sensitive calcium ch annels. The alpha-conotoxin family is represented by several peptides block ing muscular or neuronal nicotinic acetylcholine receptors. Finally a block er of potassium channels is presented as well as two conotoxins acting on t he N-Methyl-D-Aspartate receptor. Primary structures and cysteine framework s of all these conotoxins are shown and compared. At the end of the review, we report the contribution of molecular biology to identification of new c onotoxins having original pharmacological properties. In conclusion, conoto xins have received increasing attention from physiologists, pharmacologists , biochemists and physicians because of their selectivity as well as their pharmacological and therapeutic potential.