- Title:
- Lipid Modulation of Calcium Flux through CaV2.3 Regulates Acrosome Exocytosis and Fertilization
- Journal:
- Developmental Cell, Vol. 28, Issue 3, p310–321, 2014
- Author(s):
- Roy Cohen, Danielle E. Buttke, Atsushi Asano, Chinatsu Mukai, Jacquelyn L. Nelson, Dongjun Ren, Richard J. Miller, Moshe Cohen-Kutner, Atlas D, Travis AJ.
- Short description:
- Sperm function is tightly controlled by membrane lipids. Cohen et al. show that sterol efflux and focal enrichment of GM1 induce CaV2.3-mediated Ca2+ transients, spatiotemporally regulating acrosome exocytosis and fertilizing ability. They define a molecular mechanism involving both GM1's lipid and sugar moieties and the α1E and α2δ1 channel subunits.
- Link to the journal
Abstract taken from PubMed
- 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.
- Link to the paper on PubMed
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