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肝再生磷酸酶对于视网膜发育过程中光感受器细胞极性和存活至关重要。

Phosphatase of Regenerating Liver Is Critical for Photoreceptor Cell Polarity and Survival during Retinal Development.

机构信息

Department of Molecular Biology and Human Genetics, Tzu Chi University, 701 Zhongyang Rd., Sec. 3, Hualien 97004, Taiwan.

Department of Life Sciences, Tzu Chi University, 701 Zhongyang Rd., Sec. 3, Hualien 97004, Taiwan.

出版信息

Int J Mol Sci. 2023 Jul 15;24(14):11501. doi: 10.3390/ijms241411501.

Abstract

Establishing apicobasal polarity, involving intricate interactions among polarity regulators, is key for epithelial cell function. Though phosphatase of regenerating liver (PRL) proteins are implicated in diverse biological processes, including cancer, their developmental role remains unclear. In this study, we explore the role of PRL (dPRL) in photoreceptor cell development. We reveal that dPRL, requiring a C-terminal prenylation motif, is highly enriched in the apical membrane of developing photoreceptor cells. Moreover, knockdown during retinal development results in adult retinal degeneration, caused by -induced apoptosis. depletion also mislocalizes cell adhesion and polarity proteins like Armadillo, Crumbs, and DaPKC and relocates the basolateral protein, alpha subunit of Na/K-ATPase, to the presumed apical membrane. Importantly, this polarity disruption is not secondary to apoptosis, as suppressing expression does not rescue the polarity defect in -depleted photoreceptor cells. These findings underscore dPRL's crucial role in photoreceptor cell polarity and emphasize PRL's importance in establishing epithelial polarity and maintaining cell survival during retinal development, offering new insights into PRL's role in normal epithelium.

摘要

建立顶端 - 基底极性,涉及极性调节剂之间的复杂相互作用,是上皮细胞功能的关键。尽管肝再生磷酸酶(PRL)蛋白参与多种生物过程,包括癌症,但它们在发育中的作用仍不清楚。在这项研究中,我们探讨了 PRL(dPRL)在光感受器细胞发育中的作用。我们揭示了 dPRL 需要 C 末端 prenylation 基序,在发育中的光感受器细胞的顶膜中高度富集。此外,在视网膜发育过程中敲低 dPRL 会导致成年视网膜变性,这是由凋亡诱导的。dPRL 耗竭还会使细胞粘附和极性蛋白(如 Armadillo、Crums 和 DaPKC)发生错误定位,并将基底外侧蛋白,Na/K-ATPase 的 α 亚基,重新定位到假定的顶膜。重要的是,这种极性破坏不是凋亡的次要原因,因为抑制 dPRL 的表达并不能挽救在 - 耗尽的光感受器细胞中的极性缺陷。这些发现强调了 dPRL 在光感受器细胞极性中的关键作用,并强调了 PRL 在建立上皮细胞极性和维持视网膜发育过程中的细胞存活中的重要性,为 PRL 在正常上皮细胞中的作用提供了新的见解。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/58d6/10380645/db6d7487bcad/ijms-24-11501-g001.jpg

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