期刊
DEVELOPMENTAL BIOLOGY
卷 319, 期 2, 页码 211-222出版社
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.ydbio.2008.03.047
关键词
haploinsufficiency; infertility; gene targeting deletion; TSSK1; TSSK2; TSKS; spermatozoa; protein interaction; protein phosphorylation
资金
- FIC NIH HHS [D43 TW000654-10, D43 TW000654-07, D43 TW000654-09, D43 TW000654-10S1, D43 TW000654, D43 TW000654-13, D43 TW000654-11, D43 TW000654-08, D43 TW000654-12, D43 TW000654-06] Funding Source: Medline
- NCRR NIH HHS [P51 RR000166, P51 RR000166-400110, P51 RR000166-38S10110] Funding Source: Medline
- NICHD NIH HHS [U54 HD029099-090003, U54 HD029099, R03 HD055129-01, U54 HD029099-10S2, U54 HD029099-08, R03 HD055129-02, U54 HD029099-070003, U54 HD029099-10, U54 HD029099-080003, R03 HD055129, U54 HD029099-10S1, U54 HD029099-10S20003, U54 HD029099-09, U54 HD029099-10S10003, R01 HD037416, R01 HD045783, R01 HD 045783, U54 HD029099-10S3, U54 HD29099, D43 TW/HD 00654, U54 HD029099-100003, U54 HD029099-060003] Funding Source: Medline
Targeted deletion of Tssk1 and 2 resulted in male chimeras which produced sperm/spermatogenic cells bearing the mutant allele, however this allele was never transmitted to offspring, indicating infertility due to haploinsufficiency. Morphological defects in chimeras included failure to form elongated spermatids, apoptosis of spermatocytes and spermatids, and the appearance of numerous round cells in the epididymal lumen. Characterization of TSSK2 and its interactions with the substrate, TSKS, were further investigated in human and mouse. The presence of both kinase and substrate in the testis was confirmed, while persistence of both proteins in spermatozoa was revealed for the first time. In vivo binding interactions between TSSK2 and TSKS were established through co-immunoprecipitation of TSSK2/TSKS complexes from both human sperm and mouse testis extracts. A role for the human TSKS N-terminus in enzyme binding was defined by deletion mapping. TSKS immunoprecipitated from both mouse testis and human sperm extracts was actively phosphorylated. Ser281 was identified as a phosphorylation site in mouse TSKS. These results confirm both TSSK 2 and TSKS persist in sperm, define the critical role of TSKS' N-terminus in enzyme interaction, identify Ser 281 as a TSKS phosphorylation site and indicate an indispensable role for TSSK 1 and 2 in spermiogenesis. Published by Elsevier Inc.
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