LCRMP-1 对于精子发生是必需的，并通过 PI3K-Akt 通路稳定精子细胞 F-actin 的组织。
LCRMP-1 is required for spermatogenesis and stabilises spermatid F-actin organization via the PI3K-Akt pathway.
机构信息
Department of Clinical Laboratory Sciences and Medical Biotechnology, College of Medicine, National Taiwan University, Taipei, Taiwan.
Genome and Systems Biology Degree Program, National Taiwan University and Academia Sinica, Taipei, Taiwan.
出版信息
Commun Biol. 2023 Apr 10;6(1):389. doi: 10.1038/s42003-023-04778-2.
Long-form collapsin response mediator protein-1 (LCRMP-1) belongs to the CRMP family which comprises brain-enriched proteins responsible for axon guidance. However, its role in spermatogenesis remains unclear. Here we find that LCRMP-1 is abundantly expressed in the testis. To characterize its physiological function, we generate LCRMP-1-deficient mice (Lcrmp-1). These mice exhibit aberrant spermiation with apoptotic spermatids, oligospermia, and accumulation of immature testicular cells, contributing to reduced fertility. In the seminiferous epithelial cycle, LCRMP-1 expression pattern varies in a stage-dependent manner. LCRMP-1 is highly expressed in spermatids during spermatogenesis and especially localized to the spermiation machinery during spermiation. Mechanistically, LCRMP-1 deficiency causes disorganized F-actin due to unbalanced signaling of F-actin dynamics through upregulated PI3K-Akt-mTOR signaling. In conclusion, LCRMP-1 maintains spermatogenesis homeostasis by modulating cytoskeleton remodeling for spermatozoa release.
长格式卷曲相关应答介蛋白-1（LCRMP-1）属于 CRMP 家族，该家族包含负责轴突导向的脑丰富蛋白。然而，其在精子发生中的作用尚不清楚。在这里，我们发现 LCRMP-1 在睾丸中大量表达。为了表征其生理功能，我们生成了 LCRMP-1 缺失小鼠（Lcrmp-1）。这些小鼠表现出精子发生异常，有凋亡的精母细胞、少精症和未成熟睾丸细胞的积累，导致生育能力下降。在精母细胞上皮周期中，LCRMP-1 的表达模式随阶段而异。在精子发生过程中，LCRMP-1 在精母细胞中高度表达，特别是在精子发生过程中定位于精子释放的机制中。在机制上，LCRMP-1 缺失导致 F-肌动蛋白排列紊乱，原因是 F-肌动蛋白动力学的信号失衡通过上调的 PI3K-Akt-mTOR 信号传导。总之，LCRMP-1 通过调节细胞骨架重塑来维持精子发生的动态平衡，以释放精子。
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