Rajala Ammaji, Rajala Rahul, Bhat Mohd A, Eminhizer Mark, Hao Jeff, Du Jianhai, Rajala Raju V S
Department of Ophthalmology, University of Oklahoma Health Sciences Center, Oklahoma City, OK, 73104, USA.
Dean McGee Eye Institute, Oklahoma City, OK, 73104, USA.
Cell Death Dis. 2024 Aug 8;15(8):577. doi: 10.1038/s41419-024-06924-y.
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.
Shp2是一种关键的含SH2结构域的酪氨酸磷酸酶，对细胞调节至关重要，并与代谢紊乱、肥胖、糖尿病、努南综合征、豹皮综合征和癌症有关。本研究聚焦于视杆光感受器细胞中的Shp2，揭示了其富集现象，尤其是在视杆细胞中。视杆细胞中Shp2的缺失导致年龄依赖性的光感受器退化。Shp2靶向紧密连接蛋白闭合蛋白（OCLN），其缺失会降低视网膜和视网膜色素上皮（RPE）中OCLN的表达。从缺乏Shp2的视杆细胞中分离出正在进行翻译的mRNA，随后进行RNA测序，揭示了细胞周期调节的改变。此外，在缺乏Shp2的视网膜细胞中观察到视网膜代谢改变。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。
