RRC ID |
68744
|
著者 |
Ikawa M, Tokuhiro K, Yamaguchi R, Benham AM, Tamura T, Wada I, Satouh Y, Inoue N, Okabe M.
|
タイトル |
Calsperin is a testis-specific chaperone required for sperm fertility.
|
ジャーナル |
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.
|
巻・号 |
286(7)
|
ページ |
5639-46
|
公開日 |
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
|
リソース情報 |
遺伝子材料 |
pCAG1.1 (RDB19246) |