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

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

Research output: Contribution to journalArticle

11 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)2872-2882
Number of pages11
JournalFASEB Journal
Volume29
Issue number7
DOIs
Publication statusPublished - 1 Jul 2015
Externally publishedYes

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Dynamins
Glycogen Synthase Kinase 3
Phosphorylation
Exocytosis
Spermatozoa
Acrosome Reaction
Protein Kinases
Sperm Maturation
Sperm Head
GTP Phosphohydrolases
Fertilization in Vitro
Fertilization
Germ Cells
Serine
Inhibitory Concentration 50
Cells

Cite this

Reid, A. T., Anderson, A. L., Roman, S. D., McLaughlin, E. A., McCluskey, A., Robinson, P. J., ... Nixon, B. (2015). Glycogen synthase kinase 3 regulates acrosomal exocytosis in mouse spermatozoa via dynamin phosphorylation. FASEB Journal, 29(7), 2872-2882. https://doi.org/10.1096/fj.14-265553
Reid, Andrew T. ; Anderson, Amanda L. ; Roman, Shaun D. ; McLaughlin, Eileen A. ; McCluskey, Adam ; Robinson, Phillip J. ; Aitken, R. John ; Nixon, Brett. / Glycogen synthase kinase 3 regulates acrosomal exocytosis in mouse spermatozoa via dynamin phosphorylation. In: FASEB Journal. 2015 ; Vol. 29, No. 7. pp. 2872-2882.
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Reid, AT, Anderson, AL, Roman, SD, McLaughlin, EA, McCluskey, A, Robinson, PJ, Aitken, RJ & Nixon, B 2015, 'Glycogen synthase kinase 3 regulates acrosomal exocytosis in mouse spermatozoa via dynamin phosphorylation', FASEB Journal, vol. 29, no. 7, pp. 2872-2882. https://doi.org/10.1096/fj.14-265553

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.

In: FASEB Journal, Vol. 29, No. 7, 01.07.2015, p. 2872-2882.

Research output: Contribution to journalArticle

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Reid AT, Anderson AL, Roman SD, McLaughlin EA, McCluskey A, Robinson PJ et al. Glycogen synthase kinase 3 regulates acrosomal exocytosis in mouse spermatozoa via dynamin phosphorylation. FASEB Journal. 2015 Jul 1;29(7):2872-2882. https://doi.org/10.1096/fj.14-265553