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(55) COMPLEXIN 1 IS REQUIRED FOR MAMMALIAN SPERM ACROSOMAL EXOCYTOSIS. Zhao, Longmei1, Burkin, Heather1, Reim, Kerstin2, Brose, Nils2, Miller, David1, 1 University of Illinois at Urbana-Champaign, Urbana, IL2 Max-Plank-Institute for Experimental Medicine, Göttingen, Germany ABSTRACT- Upon adhesion to the zona pellucida, sperm undergo regulated exocytosis of the acrosome, a single large vesicle. The acrosome reaction is necessary for sperm to penetrate the zona pellucida and fertilize an oocyte. Despite the difference in size, secretion dynamics and vesicle morphology, some parallels can be drawn between the sperm acrosome reaction and synaptic vesicle exocytosis. During both events, increased cytoplasmic calcium and the formation of a highly stable protein complex known as the SNARE complex appear important for membrane fusion and exocytosis. Complexin 1 and 2 are highly related cytosolic proteins that bind tightly to the assembled SNARE complex and promote neuronal exocytosis. Here we show by PCR that both complexin genes are transcribed in testicular tissue. In situ hybridization revealed transcripts for each complexin in spermatocytes. Both proteins were found in spermatids and localized to the acrosomal region of sperm. Following the acrosome reaction, complexin antibodies did not detect complexin in sperm. Two different experiments suggested that complexin 1 was necessary for the acrosome reaction. First, antibodies to complexins blocked the acrosome reaction in a dose-dependent manner. Second, sperm from mice lacking complexin 1 were unable to undergo acrosomal exocytosis in response to calcium ionophore, although spermatogenesis, sperm morphology and motility appeared normal. Complexin 2 knockout mice have normal fertility. In combination with studies of neurons, these data demonstrate that complexin 1 regulates vesicle fusion in two related but morphologically distinct secretory processes downstream of increased cytosolic calcium. Acrosomal exocytosis is unusual because complexin 2 is not sufficient to promote release of this vesicle. KEY WORDS: acrosome, vesicle, zona pellucida, fertilization |
