RRC ID 68744
Author Ikawa M, Tokuhiro K, Yamaguchi R, Benham AM, Tamura T, Wada I, Satouh Y, Inoue N, Okabe M.
Title Calsperin is a testis-specific chaperone required for sperm fertility.
Journal J Biol Chem
Abstract Calnexin (CANX) and calreticulin (CALR) are homologous lectin chaperones located in the endoplasmic reticulum and cooperate to mediate nascent glycoprotein folding. In the testis, calmegin (CLGN) and calsperin (CALR3) are expressed as germ cell-specific counterparts of CANX and CALR, respectively. Here, we show that Calr3(-/-) males produced apparently normal sperm but were infertile because of defective sperm migration from the uterus into the oviduct and defective binding to the zona pellucida. Whereas CLGN was required for ADAM1A/ADAM2 dimerization and subsequent maturation of ADAM3, a sperm membrane protein required for fertilization, we show that CALR3 is a lectin-deficient chaperone directly required for ADAM3 maturation. Our results establish the client specificity of CALR3 and demonstrate that the germ cell-specific CALR-like endoplasmic reticulum chaperones have contrasting functions in the development of male fertility. The identification and understanding of the maturation mechanisms of key sperm proteins will pave the way toward novel approaches for both contraception and treatment of unexplained male infertility.
Volume 286(7)
Pages 5639-46
Published 2011-2-18
DOI 10.1074/jbc.M110.140152
PII S0021-9258(20)52134-0
PMID 21131354
PMC PMC3037677
MeSH ADAM Proteins / genetics ADAM Proteins / metabolism Animals Calbindin 2 Endoplasmic Reticulum / genetics Endoplasmic Reticulum / metabolism Female Fertility / physiology* Infertility, Male / genetics Infertility, Male / metabolism Male Mice Mice, Knockout Organ Specificity / physiology S100 Calcium Binding Protein G / genetics S100 Calcium Binding Protein G / metabolism* Sperm Motility / physiology* Sperm-Ovum Interactions / physiology* Spermatozoa / metabolism* Testis / metabolism* Zona Pellucida / metabolism
IF 4.238
DNA material pCAG1.1 (RDB19246)