Glycogen synthase kinase 3 regulates acrosomal exocytosis in mouse spermatozoa via dynamin phosphorylation

Reid, Andrew T.; Anderson, Amanda L.; Roman, Shaun D.; McLaughlin, Eileen A.; McCluskey, Adam; Robinson, Phillip J.; Aitken, R. John; Nixon, Brett

Title: Glycogen synthase kinase 3 regulates acrosomal exocytosis in mouse spermatozoa via dynamin phosphorylation
Creator: Reid, Andrew T.; Anderson, Amanda L.; Roman, Shaun D.; McLaughlin, Eileen A.; McCluskey, Adam; Robinson, Phillip J.; Aitken, R. John; Nixon, Brett
Relation: NHMRC
Relation: FASEB Journal Vol. 29, Issue 7, p. 2872-2882
Publisher Link: http://dx.doi.org/10.1096/fj.14-265553
Publisher: Federation of American Societies for Experimental Biology
Resource Type: journal article
Date: 2015
Description: The dynamin family of GTPases has been implicated as novel regulators of the acrosome reaction, a unique exocytotic event that is essential for fertilization. Dynamin activity during the acrosome reaction is accompanied by phosphorylation of key serine residues. We now tested the hypothesis that glycogen synthase kinase 3 (GSK3) is the protein kinase responsible for dynamin phosphorylation at these phosphosites in mouse spermatozoa. Pharmacologic inhibition of GSK3 in mature mouse spermatozoa (CHIR99021: IC₅₀ = 6.7 nM) led to a significant reduction in dynamin phosphorylation (10.3% vs. 27.3%; P < 0.001), acrosomal exocytosis (9.7% vs. 25.7%; P < 0.01), and in vitro fertilization (53% vs. 100%; P < 0.01). GSK3 was shown to be present in developing germ cells where it colocalized with dynamin in the peri-acrosomal domain. However, additional GSK3 was acquired by maturing mouse spermatozoa within the male reproductive tract, via a novel mechanism involving direct interaction of sperm heads with extracellular structures known as epididymal dense bodies. These data reveal a novel mode for the cellular acquisition of a protein kinase and identify a key role for GSK3 in the regulation of sperm maturation and acrosomal exocytosis.—Reid, A. T., Anderson, A. L., Roman, S. D., McLaughlin, E. A., McCluskey, A., Robinson, P. J., Aitken, R. J., Nixon, B. Glycogen synthase kinase 3 regulates acrosomal exocytosis in mouse spermatozoa via dynamin phosphorylation.
Subject: acrosome reaction; sperm maturation; epididymal dense bodies
Identifier: http://hdl.handle.net/1959.13/1338205
Identifier: uon:27976
Identifier: ISSN:0892-6638
Language: eng
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