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首页> 外文期刊>AIMS Genetics >Expression characterization and functional implication of the collagen-modifying Leprecan proteins in mouse gonadal tissue and mature sperm
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Expression characterization and functional implication of the collagen-modifying Leprecan proteins in mouse gonadal tissue and mature sperm

机译：胶原蛋白修饰的妖精蛋白在小鼠性腺组织和成熟精子中的表达特征和功能意义

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The Leprecan protein family which includes the prolyl 3-hydroxylase enzymes (P3H1, P3H2, and P3H3), the closely related cartilage-associated protein (CRTAP), and SC65 (Synaptonemal complex 65, aka P3H4, LEPREL4), is involved in the post-translational modification of fibrillar collagens. Mutations in CRTAP , P3H1 and P3H2 cause human genetic diseases. We recently showed that SC65 forms a stable complex in the endoplasmic reticulum with P3H3 and lysyl hydroxylase 1 and that loss of this complex leads to defective collagen lysyl hydroxylation and causes low bone mass and skin fragility. Interestingly, SC65 was initially described as a synaptonemal complex-associated protein, suggesting a potential additional role in germline cells. In the present study, we describe the expression of SC65, CRTAP and other Leprecan proteins in postnatal mouse reproductive organs. We detect SC65 expression in peritubular cells of testis up to 4 weeks of age but not in cells within seminiferous tubules, while its expression is maintained in ovarian follicles until adulthood. Similar to bone and skin, SC65 and P3H3 are also tightly co-expressed in testis and ovary. Moreover, we show that CRTAP, a protein normally involved in collagen prolyl 3-hydroxylation, is highly expressed in follicles and stroma of the ovary and in testes interstitial cells at 4 weeks of age, germline cells and mature sperm. Importantly, CrtapKO mice have a mild but significant increase in morphologically abnormal mature sperm (17% increase compared to WT). These data suggest a role for the Leprecans in the post-translational modification of collagens expressed in the stroma of the reproductive organs. While we could not confirm that SC65 is part of the synaptonemal complex, the expression of CRTAP in the seminiferous tubules and in mature sperm suggest a role in the testis germ cell lineage and sperm morphogenesis.
机译：Leprecan蛋白家族包括脯氨酰3-羟化酶（P3H1，P3H2和P3H3），密切相关的软骨相关蛋白（CRTAP）和SC65（突触复合体65，又名P3H4，LEPREL4）。 -原纤维胶原的翻译修饰。 CRTAP，P3H1和P3H2中的突变会导致人类遗传病。我们最近发现，SC65与P3H3和赖氨酰羟化酶1在内质网中形成稳定的复合物，这种复合物的丢失会导致胶原赖氨酰羟化缺陷，并导致骨量低和皮肤脆弱。有趣的是，SC65最初被描述为突触复合物相关蛋白，提示在种系细胞中潜在的额外作用。在本研究中，我们描述了SC65，CRTAP和其他Leprecan蛋白在出生后小鼠生殖器官中的表达。我们检测到SC65在最多4周龄的睾丸周围细胞中表达，但在生精小管内的细胞中未检测到，而其表达在卵巢卵泡中一直保持到成年。与骨骼和皮肤相似，SC65和P3H3在睾丸和卵巢中也紧密共表达。此外，我们显示CRTAP，通常参与胶原脯氨酰3-羟基化的蛋白质，在4周龄的卵泡和间质以及睾丸间质细胞，种系细胞和成熟精子中高表达。重要的是，CrtapKO小鼠的形态异常成熟精子有轻度但显着的增加（与WT相比增加了17％）。这些数据表明，妖精蛋白在生殖器官基质中表达的胶原蛋白的翻译后修饰中起作用。虽然我们无法确定SC65是突触复合物的一部分，但CRTAP在生精小管和成熟精子中的表达暗示了在睾丸生殖细胞谱系和精子形态发生中的作用。

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