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A Novel Role for Nonmuscle Myosin II-A in Sperm Development

Thursday, September 17, 2015 — Poster Session II

12:00 p.m. – 1:30 p.m.
FAES Terrace
NHLBI
DEVBIO-6

Authors

  • CB Lerma Cervantes
  • K Tokuhiro
  • N Billington
  • A Wang
  • Y Zhang
  • MA Conti
  • MJ Kelley
  • MP Daniels
  • JR Sellers
  • J Dean
  • RS Adelstein

Abstract

Sperm head shaping is dependent upon the constriction of F-actin bundles found in the Sertoli cells of the testes as well as the presence of the acroplaxome, a cytoskeletal plate that is surrounded by a marginal ring. The acroplaxome anchors the acrosomal vesicle to the sperm nuclear envelope. Spermiogenesis refers to these differentiation processes and the coupling of the tail to the sperm head. Herein we describe a mouse line with a mutation in nonmuscle myosin II-A (NM II-A), E1841K, found in human MYH9-related disease. In addition to modeling MYH9-related disease, male mice homozygous for the mutation (AE1841K/AE1841K) are infertile with essentially no viable sperm in the epididymis. Histological analyses reveal severe sperm defects in the AE1841K/AE1841K mouse testes that begin during spermiogenesis. Transmission electron microscopy shows aberrant spermatid elongation whereby the acroplaxome and the acrosome fail to correctly extend and often show an irregular wavy appearance. These aberrantly elongated spermatids fail to couple the developing tail to the spermatid head. Immunofluorescence confocal microscopy of developing spermatids shows localization of both wild-type and mutant NM II-A to the marginal ring of the acroplaxome. Further, in vitro experiments using baculovirus-expressed NM II show abnormal filament formation of the NM II-A E1841K. The filaments formed by the mutant myosin are longer than wild-type filaments and tend to form aggregates. The results suggest that the mutant NM II-A filaments form a defective marginal ring leading to abnormal sperm head shaping, thus revealing a previously unknown role for NM II-A in sperm development.

Category: Developmental Biology