Mesh : Animals Retinal Degeneration / pathology metabolism genetics Protein Tyrosine Phosphatase, Non-Receptor Type 11 / metabolism genetics Mice Retinal Rod Photoreceptor Cells / metabolism pathology Retinal Pigment Epithelium / metabolism pathology Mice, Knockout Aging / metabolism genetics Occludin / metabolism genetics Mice, Inbred C57BL Gene Deletion Retina / metabolism pathology

来  源:   DOI:10.1038/s41419-024-06924-y   PDF(Pubmed)

Abstract:
Shp2, a critical SH2-domain-containing tyrosine phosphatase, is essential for cellular regulation and implicated in metabolic disruptions, obesity, diabetes, Noonan syndrome, LEOPARD syndrome, and cancers. This study focuses on Shp2 in rod photoreceptor cells, revealing its enrichment, particularly in rods. Deletion of Shp2 in rods leads to age-dependent photoreceptor degeneration. Shp2 targets occludin (OCLN), a tight junction protein, and its deletion reduces OCLN expression in the retina and retinal pigment epithelium (RPE). The isolation of actively translating mRNAs from rods lacking Shp2, followed by RNA sequencing, reveals alterations in cell cycle regulation. Additionally, altered retinal metabolism is observed in retinal cells lacking Shp2. Our studies indicate that Shp2 is crucial for maintaining the structure and function of photoreceptors.
摘要:
Shp2,一种关键的含SH2结构域的酪氨酸磷酸酶,对细胞调节至关重要,并参与代谢破坏,肥胖,糖尿病,努南综合征,LEOPARD综合征,和癌症。本研究集中在视杆感光细胞中的Shp2,揭示了它的丰富,尤其是棒。视杆中Shp2的缺失导致年龄依赖性光感受器变性。Shp2目标闭塞蛋白(OCLN),一种紧密连接的蛋白质,其缺失降低了OCLN在视网膜和视网膜色素上皮(RPE)中的表达。从缺乏Shp2的杆状物中分离主动翻译的mRNA,然后进行RNA测序,揭示了细胞周期调节的变化。此外,在缺乏Shp2的视网膜细胞中观察到改变的视网膜代谢。我们的研究表明,Shp2对于维持光感受器的结构和功能至关重要。
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