Calpain modulates capacitation and acrosome reaction through cleavage of the spectrin cytoskeleton.
Research on fertilization in mammalian species has revealed that Ca(2+) is an important player in biochemical and physiological events enabling the sperm to penetrate the oocyte. Ca(2+) is a signal transducer that particularly mediates capacitation and acrosome reaction (AR). Before becoming fertilization competent, sperm must experience several molecular, biochemical, and physiological changes where Ca(2+) plays a pivotal role. Calpain-1 and calpain-2 are Ca(2+)-dependent proteases widely studied in mammalian sperm; they have been involved in capacitation and AR but little is known about their mechanism. In this work, we establish the association of calpastatin with calpain-1 and the changes undergone by this complex during capacitation in guinea pig sperm. We found that calpain-1 is relocated and translocated from cytoplasm to plasma membrane (PM) during capacitation, where it could cleave spectrin, one of the proteins of the PM-associated cytoskeleton, and facilitates AR. The aforementioned results were dependent on the calpastatin phosphorylation and the presence of extracellular Ca(2+). Our findings underline the contribution of the sperm cytoskeleton in the regulation of both capacitation and AR. In addition, our findings also reveal one of the mechanisms by which calpain and calcium exert its function in sperm.
Bastián
Yadira
Y
Deparment of Biology, McGill University, Montreal, Quebec, Canada.
Roa-Espitia
Ana L
AL
Mújica
Adela
A
Hernández-González
Enrique O
EO
D020101:Acrosome Reaction / Q000502:physiology*; D000818:Animals; D015153:Blotting, Western; D002135:Calcium-Binding Proteins / Q000502:physiology; D002154:Calpain / Q000037:antagonists & inhibitors / Q000502:physiology*; D003599:Cytoskeleton / Q000502:physiology* / Q000648:ultrastructure; D004151:Dipeptides / Q000494:pharmacology; D006168:Guinea Pigs; D007976:Leupeptins / Q000494:pharmacology; D008297:Male; D008854:Microscopy, Electron; D013049:Spectrin / Q000502:physiology*; D013075:Sperm Capacitation / Q000502:physiology*; D013094:Spermatozoa / Q000502:physiology*
D002135:Calcium-Binding Proteins; D004151:Dipeptides; D007976:Leupeptins; C063261:acetylleucyl-leucyl-norleucinal; D013049:Spectrin; C071482:calpeptin; C033668:calpastatin; D002154:Calpain