التفاصيل البيبلوغرافية
| العنوان: |
DARPP32, a target of hyperactive mTORC1 in the retinal pigment epithelium. |
| المؤلفون: |
Jiyang Cai1, Litwin, Christopher2,3, Rui Cheng4, Jian-Xing Ma4, Yan Chen2,3,5 yan-chen@ouhsc.edu |
| المصدر: |
Proceedings of the National Academy of Sciences of the United States of America. 8/16/2022, Vol. 119 Issue 33, p1-3. 8p. |
| مصطلحات موضوعية: |
*RHODOPSIN, *MACULAR degeneration, *EPITHELIUM, *RETINAL degeneration, *MOLECULAR weights |
| مستخلص: |
The mechanistic target of rapamycin (mTOR) is assembled into signaling complexes of mTORC1 or mTORC2, and plays key roles in cell metabolism, stress response, and nutrient and growth factor sensing. Accumulating evidence from human and animal model studies has demonstrated a pathogenic role of hyperactive mTORC1 in agerelated macular degeneration (AMD). The retinal pigment epithelium (RPE) is a primary injury site in AMD. In mouse models of RPE-specific deletion of Tuberous sclerosis 1 (Tsc1), which encodes an upstream suppressor of mTORC1, the hyperactivated mTORC1 metabolically reprogrammed the RPE and led to the degeneration of the outer retina and choroid (CH). In the current study, we use single-cell RNA sequencing (scRNA-seq) to identify an RPE mTORC1 downstream protein, dopamineand cyclic AMP-regulated phosphoprotein of molecular weight 32,000 (DARPP-32). DARPP-32 was not found in healthy RPE but localized to drusen and basal linear deposits in human AMD eyes. In animal models, overexpressing DARPP-32 by adenoassociated virus (AAV) led to abnormal RPE structure and function. The data indicate that DARPP-32 is a previously unidentified signaling protein subjected to mTORC1 regulation and may contribute to RPE degeneration in AMD. [ABSTRACT FROM AUTHOR] |
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