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Lipid Regulation of Acrosome Exocytosis

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Part of the Advances in Anatomy, Embryology and Cell Biology book series (ADVSANAT, volume 220)

Abstract

Lipids are critical regulators of mammalian sperm function, first helping prevent premature acrosome exocytosis, then enabling sperm to become competent to fertilize at the right place/time through the process of capacitation, and ultimately triggering acrosome exocytosis. Yet because they do not fit neatly into the “DNA–RNA–protein” synthetic pathway, they are understudied and poorly understood. Here, we focus on three lipids or lipid classes—cholesterol, phospholipids, and the ganglioside GM1—in context of the modern paradigm of acrosome exocytosis. We describe how these various species are precisely segregated into membrane macrodomains and microdomains, simultaneously preventing premature exocytosis while acting as foci for organizing regulatory and effector molecules that will enable exocytosis. Although the mechanisms responsible for these domains are poorly defined, there is substantial evidence for their composition and functions. We present diverse ways that lipids and lipid modifications regulate capacitation and acrosome exocytosis, describing in more detail how removal of cholesterol plays a master regulatory role in enabling exocytosis through at least two complementary pathways. First, cholesterol efflux leads to proteolytic activation of phospholipase B, which cleaves both phospholipid tails. The resultant changes in membrane curvature provide a mechanism for the point fusions now known to occur far before a sperm physically interacts with the zona pellucida. Cholesterol efflux also enables GM1 to regulate the voltage-dependent cation channel, CaV2.3, triggering focal calcium transients required for acrosome exocytosis in response to subsequent whole-cell calcium rises. We close with a model integrating functions for lipids in regulating acrosome exocytosis.

Keywords

Zona Pellucida Cholesterol Efflux Membrane Raft Cholesterol Sulfate Acrosome Exocytosis 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.
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Notes

Acknowledgments

This work was supported by Cornell’s Baker Institute for Animal Health, the College of Veterinary Medicine, and Atkinson Center for a Sustainable Future. A.J.T. is a founder and an officer of Androvia LifeSciences, LLC, a biotechnology company investigating solutions for male infertility.

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© Springer International Publishing Switzerland 2016

Authors and Affiliations

  1. 1.Baker Institute for Animal Health, Cornell UniversityIthacaUSA
  2. 2.Atkinson Center for a Sustainable Future, Cornell UniversityIthacaUSA

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