Click here to close Hello! We notice that you are using Internet Explorer, which is not supported by Xenbase and may cause the site to display incorrectly. We suggest using a current version of Chrome, FireFox, or Safari.
XB-ART-48553
Dev Cell 2014 Feb 10;283:310-21. doi: 10.1016/j.devcel.2014.01.005.
Show Gene links Show Anatomy links

Lipid modulation of calcium flux through CaV2.3 regulates acrosome exocytosis and fertilization.

Cohen R , Buttke DE , Asano A , Mukai C , Nelson JL , Ren D , Miller RJ , Cohen-Kutner M , Atlas D , Travis AJ .


???displayArticle.abstract???
Membrane lipid regulation of cell function is poorly understood. In early development, sterol efflux and the ganglioside GM1 regulate sperm acrosome exocytosis (AE) and fertilization competence through unknown mechanisms. Here, we show that sterol efflux and focal enrichment of GM1 trigger Ca(2+) influx necessary for AE through CaV2.3, whose activity has been highly controversial in sperm. Sperm lacking CaV2.3's pore-forming α1E subunit showed altered Ca(2+) responses, reduced AE, and a strong subfertility phenotype. Surprisingly, AE depended on spatiotemporal information encoded by flux through CaV2.3, not merely the presence/amplitude of Ca(2+) waves. Using studies in both sperm and voltage clamp of Xenopus oocytes, we define a molecular mechanism for GM1/CaV2.3 regulatory interaction, requiring GM1's lipid and sugar components and CaV2.3's α1E and α2δ subunits. Our results provide a mechanistic understanding of membrane lipid regulation of Ca(2+) flux and therefore Ca(2+)-dependent cellular and developmental processes such as exocytosis and fertilization.

???displayArticle.pubmedLink??? 24525187
???displayArticle.pmcLink??? PMC3947087
???displayArticle.link??? Dev Cell
???displayArticle.grants??? [+]

Species referenced: Xenopus laevis
Genes referenced: cacna1e cav2

References [+] :
Albillos, R-Type Ca2+ channels are coupled to the rapid component of secretion in mouse adrenal slice chromaffin cells. 2000, Pubmed