June 2023
Volume 64, Issue 8
Open Access
ARVO Annual Meeting Abstract  |   June 2023
MYPT1 Dephosphorylates HMGA1a to Regulates p53-Mediated Apoptosis in Zebrafish Retina and Lens
Author Affiliations & Notes
  • Xuebin Hu
    Sun Yat-Sen University Zhongshan Ophthalmic Center State Key Laboratory of Ophthalmology, Guangzhou, Guangdong, China
  • LAN ZHANG
    Sun Yat-Sen University Zhongshan Ophthalmic Center State Key Laboratory of Ophthalmology, Guangzhou, Guangdong, China
  • Jialing Fu
    Sun Yat-Sen University Zhongshan Ophthalmic Center State Key Laboratory of Ophthalmology, Guangzhou, Guangdong, China
  • Yan Wang
    Sun Yat-Sen University Zhongshan Ophthalmic Center State Key Laboratory of Ophthalmology, Guangzhou, Guangdong, China
  • Shuyu Zheng
    Sun Yat-Sen University Zhongshan Ophthalmic Center State Key Laboratory of Ophthalmology, Guangzhou, Guangdong, China
  • Jingmiao Wang
    Sun Yat-Sen University Zhongshan Ophthalmic Center State Key Laboratory of Ophthalmology, Guangzhou, Guangdong, China
  • yuan xiao
    Sun Yat-Sen University Zhongshan Ophthalmic Center State Key Laboratory of Ophthalmology, Guangzhou, Guangdong, China
  • Xinmiao Liang
    Sun Yat-Sen University Zhongshan Ophthalmic Center State Key Laboratory of Ophthalmology, Guangzhou, Guangdong, China
  • yuwen gan
    Sun Yat-Sen University Zhongshan Ophthalmic Center State Key Laboratory of Ophthalmology, Guangzhou, Guangdong, China
  • David W Li
    Sun Yat-Sen University Zhongshan Ophthalmic Center State Key Laboratory of Ophthalmology, Guangzhou, Guangdong, China
  • Footnotes
    Commercial Relationships   Xuebin Hu None; LAN ZHANG None; Jialing Fu None; Yan Wang None; Shuyu Zheng None; Jingmiao Wang None; yuan xiao None; Xinmiao Liang None; yuwen gan None; David Li None
  • Footnotes
    Support  Supported by National Natural Science Foundation of China (Grants 81970784, 81970787, 82271071,) and the Joint Key Project from the Natural Science Foundation of Guangdong Province and Guangzhou City (2019B1515120014),and the Fundamental Funds of the State Key Laboratory of Ophthalmology of Zhongshan Ophthalmic Center (3030901010110 and 3030901010111)
Investigative Ophthalmology & Visual Science June 2023, Vol.64, 3638. doi:
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      Xuebin Hu, LAN ZHANG, Jialing Fu, Yan Wang, Shuyu Zheng, Jingmiao Wang, yuan xiao, Xinmiao Liang, yuwen gan, David W Li; MYPT1 Dephosphorylates HMGA1a to Regulates p53-Mediated Apoptosis in Zebrafish Retina and Lens. Invest. Ophthalmol. Vis. Sci. 2023;64(8):3638.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Purpose : Myosin phosphatase targeting subunit 1 (Mypt1) is the regulatory subunit of myosin phosphatase which dephosphorylates the light chain of myosin II to inhibit its contraction. Although biochemical properties of Mypt1 have been characterized in detail, its biological functions in eye development are not well understood.

Methods : CRISPR/Cas9 technology was used to knockout mypt1 in zebrafish. phosphoproteomics analysis was used to detect the phosphorylation status changes of the MYPT1 target proteins. Immunofluorescence, immunoprecipitation and RT-qPCR analysis were used to detect changes of gene expression.

Results : We generated a mypt1 knockout model in zebrafish. Knockout of mypt1 caused microphthalmia in zebrafish during early development. In mypt1 knockout zebrafish, differentiation of retina was affected, and the size of lens was smaller. Width of inner and outer plexiform layers were both thinner in mypt1 knockout zebrafish and the development of outer segment in photoreceptor was disrupted. Phosphoproteomics results showed that the phosphorylation of HMGA1a (High Mobility Group Protein A1a) was increased in mypt1 knockout zebrafish. We showed that mypt1 interacted with HMGA1a and regulated the dephosphorylation of HMGA1a by in vitro experiment. Phosphorylation of HMGA1a inhibits HMGA1a-P53 interaction and modulated the transcriptional function of p53. In mypt1 knockout zebrafish, the expression of p53 regulated genes was up-regulated and apoptosis signals were increased in mypt1 knockout retinas and lens.

Conclusions : Our results suggest that mypt1 regulates the transcriptional activity of p53 by dephosphorylating HMGA1a during early eye development in zebrafish. These findings provide important information on functions of protein phosphorylation and dephosphorylation during eye development.

This abstract was presented at the 2023 ARVO Annual Meeting, held in New Orleans, LA, April 23-27, 2023.

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