TEX38 localizes ZDHHC19 to the plasma membrane and regulates sperm head morphogenesis in mice

• 成果类型: Article
• 署名作者: Kaneda, Yuki; Lu, Yonggang; Sun, Jiang; Shimada, Keisuke; Emori, Chihiro; Noda, Taichi; Koyano, Takayuki; Matsuyama, Makoto; Miyata, Haruhiko; Ikawa, Masahito
• 署名单位: University of Osaka; University of Osaka; University of Osaka; Kumamoto University; Kumamoto University; University of Tokyo; University of Osaka; University of Osaka
• 刊物名称: PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
• ISSN/ISSBN: 0027-11069
• DOI: 10.1073/pnas.2417943122
• 发表日期: 2025-03-03
• 关键词: cytoplasmic droplet; lumen polarity; mouse sperm; spermatogenesis; palmitoylation; spermatozoa; proteins; kinases; cycle

摘要

Sperm morphogenesis is a tightly regulated differentiation process, disruption of which leads to sperm malfunction and male infertility. Here, we show that Tex38 knockout (KO) male mice are infertile. Tex38 KO spermatids exhibit excess retention of residual cytoplasm around the head, resulting in abnormal sperm morphology with backward head bending. TEX38 interacts and colocalizes with ZDHHC19, a testis- enriched acyltransferase catalyzing protein S- palmitoylation, at the plasma membrane of spermatids. ZDHHC19 and TEX38 are each downregulated in mouse testes lacking the other protein. TEX38 stabilizes and localizes ZDHHC19 to the plasma membrane of cultured cells and vice versa, consolidating their interdependence. Mice deficient in ZDHHC19 or harboring a C142S mutation that disables the palmitoyltransferase activity of ZDHHC19 display phenotypes resembling those of Tex38 KO mice. Strikingly, ZDHHC19 palmitoylates ARRDC5, an arrestin family protein regulating sperm differentiation. Overall, our findings indicate that TEX38 forms a stable complex with ZDHHC19 at the plasma membrane of spermatids, which governs downstream S- palmitoylation of proteins essential for morphological transformation of spermatids.