Cholesterol is critical to the integrity of neuronal porosome/fusion pore.
Secretion is one of the most fundamental cellular processes. Porosomes have been demonstrated as the universal secretory machinery in cells. Earlier studies determine the presence of a number of proteins in porosomes, among them the N- and P/Q-type calcium channels, actin, syntaxin-1, synaptotagmin-1, vimentin, the N-ethylmaleimide-sensitive factor (NSF), the chloride channel CLC-3, and the alpha subunit of the heterotrimeric GTP-binding protein G(o). Studies demonstrate that t-SNAREs localize at the base of porosomes, and directly interact with calcium channels. In the present study, we demonstrate that Syntaxin-1 co-localizes with cholesterol in solubilized synaptosomal membrane preparations. Depletion of cholesterol, results in the dissociation of both Syntaxin-1 and N-type calcium channel from neuronal porosomes. Thus, cholesterol participates as an integral component of the neuronal porosome complex, and is required for its stability.
Jeremic
Aleksandar
A
Department of Physiology, Wayne State University School of Medicine, Detroit, MI, 48201, USA.
Jin Cho
Won
W
Jena
Bhanu P
BP
D000818:Animals; D001921:Brain / Q000648:ultrastructure; D020864:Calcium Channels, N-Type / Q000378:metabolism; D002462:Cell Membrane / Q000378:metabolism* / Q000648:ultrastructure*; D002784:Cholesterol / Q000378:metabolism / Q000502:physiology*; D003034:Coated Pits, Cell-Membrane / Q000378:metabolism / Q000648:ultrastructure*; D005089:Exocytosis; D008074:Lipoproteins / Q000378:metabolism*; D009474:Neurons / Q000737:chemistry / Q000648:ultrastructure*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013572:Synaptic Vesicles / Q000648:ultrastructure*; D050827:Syntaxin 1 / Q000378:metabolism
D020864:Calcium Channels, N-Type; D008074:Lipoproteins; D050827:Syntaxin 1; D002784:Cholesterol