RRC ID 68745
Author Ikawa M, Nakanishi T, Yamada S, Wada I, Kominami K, Tanaka H, Nozaki M, Nishimune Y, Okabe M.
Title Calmegin is required for fertilin alpha/beta heterodimerization and sperm fertility.
Journal Dev Biol
Abstract Loss of the endoplasmic reticulum resident chaperone calmegin leads to the production of sterile sperm that do not bind to the egg zona pellucida (M. Ikawa et al., 1997, Nature 387, 607-611). In the present study, we demonstrate that calmegin -/- sperm were defective in migrating into the oviducts and in binding to the egg plasma membrane. Despite the impaired adhesive function, calmegin -/- sperm could fertilize eggs when zonae pellucidae were partially dissected, and eggs fertilized in this manner could develop normally to term. Since these sperm characteristics were similar to those found in fertilin beta -/- sperm, we investigated the interaction of calmegin with fertilin beta. Using immunoprecipitation techniques, calmegin was found to bind to sperm membrane proteins, fertilin alpha and beta, during spermatogenesis. The binding was specific to calmegin: another endoplasmic reticulum chaperone calnexin, a calmegin homologue, was not able to bind to fertilin alpha and beta. In the calmegin -/- mice, a loss of heterodimerization of fertilin alpha and beta was observed and fertilin beta was not detectable in mature sperm. The data not only explain why the calmegin and fertilin beta knockout mouse lines share a common infertile phenotype, but also reveal the importance of the maturation of sperm membrane proteins in the endoplasmic reticulum.
Volume 240(1)
Pages 254-61
Published 2001-12-1
DOI 10.1006/dbio.2001.0462
PII S0012-1606(01)90462-2
PMID 11784061
MeSH ADAM Proteins Animals Base Sequence Calcium-Binding Proteins / genetics Calcium-Binding Proteins / metabolism Calcium-Binding Proteins / physiology* Calnexin* DNA Primers Dimerization Endoplasmic Reticulum / metabolism Female Fertilins Male Membrane Glycoproteins / metabolism* Membrane Proteins / genetics Membrane Proteins / metabolism Membrane Proteins / physiology* Metalloendopeptidases / metabolism* Mice Molecular Chaperones Sperm-Ovum Interactions*
IF 2.896
DNA material pClgn1.1 (RDB19247)