2025-03-04 大阪大学,科学技術振興機構
<関連情報>
- https://www.jst.go.jp/pr/announce/20250304/index.html
- https://www.jst.go.jp/pr/announce/20250304/pdf/20250304.pdf
- https://www.pnas.org/doi/10.1073/pnas.2417943122
TEX38はZDHHC19を細胞膜に局在させ、マウスの精子頭部の形態形成を制御する TEX38 localizes ZDHHC19 to the plasma membrane and regulates sperm head morphogenesis in mice
Yuki Kaneda, Yonggang Lu, Jiang Sun, +6, and Masahito Ikawa
Proceedings of the National Academy of Sciences Published:March 3, 2025
DOI:https://doi.org/10.1073/pnas.2417943122
Significance
S-palmitoylation is a lipid posttranslational modification process involved in diverse cellular events in a wide range of biological systems. It has remained unclear whether S-palmitoylation has a role in male reproduction. Here, we found that TEX38 is important for the stability and plasma membrane localization of ZDHHC19, an S-palmitoylation enzyme, in the male germ cells. Ablation of TEX38 or disruption of the palmitoylation activity of ZDHHC19 in mice resulted in sperm head malformation and male infertility. This study demonstrates the essential role of S-palmitoylation in sperm head morphogenesis. A germline-specific, ZDHHC19-mediated posttranslational modification pathway sheds light on diagnosis of idiopathic male infertility and development of nonhormonal male contraceptives.
Abstract
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.
