title: Lipid Regulation of Acrosome Exocytosis.
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 G(M1)--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 G(M1) to regulate the voltage-dependent cation channel, Ca(V)2.3, 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.
authors.affiliation: Baker Institute for Animal Health, Cornell University, Ithaca, NY, 14853, USA.
authors.forename: Roy
authors.initials: R
authors.lastname: Cohen
authors.affiliation: Baker Institute for Animal Health, Cornell University, Ithaca, NY, 14853, USA.
authors.forename: Chinatsu
authors.initials: C
authors.lastname: Mukai
authors.affiliation: Baker Institute for Animal Health, Cornell University, Ithaca, NY, 14853, USA. ajt32@cornell.edu.|Atkinson Center for a Sustainable Future, Cornell University, Ithaca, NY, 14853, USA. ajt32@cornell.edu.
authors.forename: Alexander J
authors.initials: AJ
authors.lastname: Travis
mesh_terms: D000177:Acrosome / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism*; D020101:Acrosome Reaction / Q000187:drug effects / Q000502:physiology*; D000818:Animals; D002118:Calcium / Q000378:metabolism; D020908:Calcium Channels, R-Type / Q000378:metabolism; D027682:Cation Transport Proteins / Q000819:agonists / Q000378:metabolism; D002784:Cholesterol / Q000378:metabolism* / Q000494:pharmacology; D004789:Enzyme Activation; D005089:Exocytosis / Q000187:drug effects; D005260:Female; D005677:G(M1) Ganglioside / Q000378:metabolism* / Q000494:pharmacology; D008245:Lysophospholipase / Q000378:metabolism; D008297:Male; D008561:Membrane Fusion / Q000187:drug effects / Q000502:physiology; D021962:Membrane Microdomains / Q000737:chemistry / Q000378:metabolism; D010743:Phospholipids / Q000378:metabolism* / Q000494:pharmacology; D013075:Sperm Capacitation / Q000187:drug effects / Q000502:physiology; D015044:Zona Pellucida / Q000502:physiology
chemical_list: C423009:CACNA1E protein, human; D020908:Calcium Channels, R-Type; D027682:Cation Transport Proteins; D010743:Phospholipids; D005677:G(M1) Ganglioside; D002784:Cholesterol; D008245:Lysophospholipase; D002118:Calcium