| RRC ID |
69976
|
| 著者 |
Miyata H, Oura S, Morohoshi A, Shimada K, Mashiko D, Oyama Y, Kaneda Y, Matsumura T, Abbasi F, Ikawa M.
|
| タイトル |
SPATA33 localizes calcineurin to the mitochondria and regulates sperm motility in mice.
|
| ジャーナル |
Proc Natl Acad Sci U S A
|
| Abstract |
Calcineurin is a calcium-dependent phosphatase that plays roles in a variety of biological processes including immune responses. In spermatozoa, there is a testis-enriched calcineurin composed of PPP3CC and PPP3R2 (sperm calcineurin) that is essential for sperm motility and male fertility. Because sperm calcineurin has been proposed as a target for reversible male contraceptives, identifying proteins that interact with sperm calcineurin widens the choice for developing specific inhibitors. Here, by screening the calcineurin-interacting PxIxIT consensus motif in silico and analyzing the function of candidate proteins through the generation of gene-modified mice, we discovered that SPATA33 interacts with sperm calcineurin via a PQIIIT sequence. Spata33 knockout mice exhibit reduced sperm motility because of an inflexible midpiece, leading to impaired male fertility, which phenocopies Ppp3cc and Ppp3r2 knockout mice. Further analysis reveals that sperm calcineurin disappears from the mitochondria in the Spata33 knockout testis. In addition, immunoprecipitation analysis indicates that sperm calcineurin interacts with not only SPATA33 but also the mitochondrial protein VDAC2. These results indicate that SPATA33 localizes calcineurin to the mitochondria and regulates sperm motility.
|
| 巻・号 |
118(35)
|
| 公開日 |
2021-8-31
|
| DOI |
10.1073/pnas.2106673118
|
| PII |
2106673118
|
| PMID |
34446558
|
| PMC |
PMC8536318
|
| MeSH |
Animals
Calcineurin / genetics
Calcineurin / metabolism*
Female
Intercellular Signaling Peptides and Proteins / physiology*
Male
Mice
Mice, Knockout
Mitochondria / metabolism*
Sperm Motility*
Spermatogenesis
Testis / physiology*
Voltage-Dependent Anion Channel 2 / genetics
Voltage-Dependent Anion Channel 2 / metabolism*
|
| IF |
9.412
|
| リソース情報 |
| 遺伝子材料 |
pCAG-mSpata33-PA (RDB19398)
pCAG-mSpata33 (P79A)-PA (RDB19399)
pCAG-mSpata33 (I81A)-PA (RDB19400)
pCAG-mSpata33 (I83A)-PA (RDB19401)
pCAG-hSPATA33-8xHIS-1D4 (RDB19402)
pCAG-hPPP3CA-FLAG (RDB19403)
pCAG-hPPP3CB-FLAG (RDB19404)
pCAG-hPPP3R1 (RDB19405) |
