Abstract
Protein serine/threonine phosphatase-1 (PP-1) is one of the key enzymes responsible for dephosphorylation in vertebrates. Protein dephosphorylation via PP-1 is implicated in many different biological processes including gene expression, cell cycle control, transformation, neuronal transmission, apoptosis, autophage and senescence. However, whether PP-1 directly controls animal development remains to be investigated. Here, we present direct evidence to show that PP-1 plays an essential role in regulating eye development of vertebrates. Using goldfish as a model system, we have shown the following novel results. First, inhibition of PP-1 activity leads to death of a majority of the treated embryos, and the survived embryos displayed severe phenotype in the eye. Second, knockdown of each catalytic subunit of PP-1 with morpholino oligomers leads to partial (PP-lα knockdown) or complete (PP-lβ or PP-lγ knockdown) death of the injected embryos. The survived embryos from PP-1α knockdown displayed clear retardation in lens differentiation. Finally, overexpression of each subunit of PP-1 also causes death of majority of the injected embryos and leads to abnormal development of goldfish eye. Mechanistically, Pax-6 is one of the major downstream targets mediating the effects of PP-1 function since the eye phenotype in Pax-6 knockdown fish is similar to that derived from overexpression of PP-1. Together, our results for the first time provide direct evidence that protein phosphatase-1 plays a key role in governing normal eye formation during goldfish development.
Keywords: Cataract, differentiation, eye development, lens, PP-1, PP-1α/β/γ, protein phosphatases, retina, retina degeneration, gene expression, cell cycle progression, transformation, neuronal transmission, apoptosis, autophage
Current Molecular Medicine
Title:Protein Serine/Threonine Phosphotase-1 is Essential in Governing Normal Development of Vertebrate Eye
Volume: 12 Issue: 10
Author(s): W.-F. Hu, D.W.-C. Li, S.-J. Liu, Y.-Z. Liu, M.-B. Yu, L.-X. Luo, X.-L. Liu, M.-X. Wu, K.-L. Wu, Z. Woodward, W.-B. Liu, X.-H. Hu, W.-K. Ji, X.-W. Zhang, L. Nie, J. Liu, H.-G. Chen, X.-C. Tang, F.-Y. Liu and Q. Yan
Affiliation:
Keywords: Cataract, differentiation, eye development, lens, PP-1, PP-1α/β/γ, protein phosphatases, retina, retina degeneration, gene expression, cell cycle progression, transformation, neuronal transmission, apoptosis, autophage
Abstract: Protein serine/threonine phosphatase-1 (PP-1) is one of the key enzymes responsible for dephosphorylation in vertebrates. Protein dephosphorylation via PP-1 is implicated in many different biological processes including gene expression, cell cycle control, transformation, neuronal transmission, apoptosis, autophage and senescence. However, whether PP-1 directly controls animal development remains to be investigated. Here, we present direct evidence to show that PP-1 plays an essential role in regulating eye development of vertebrates. Using goldfish as a model system, we have shown the following novel results. First, inhibition of PP-1 activity leads to death of a majority of the treated embryos, and the survived embryos displayed severe phenotype in the eye. Second, knockdown of each catalytic subunit of PP-1 with morpholino oligomers leads to partial (PP-lα knockdown) or complete (PP-lβ or PP-lγ knockdown) death of the injected embryos. The survived embryos from PP-1α knockdown displayed clear retardation in lens differentiation. Finally, overexpression of each subunit of PP-1 also causes death of majority of the injected embryos and leads to abnormal development of goldfish eye. Mechanistically, Pax-6 is one of the major downstream targets mediating the effects of PP-1 function since the eye phenotype in Pax-6 knockdown fish is similar to that derived from overexpression of PP-1. Together, our results for the first time provide direct evidence that protein phosphatase-1 plays a key role in governing normal eye formation during goldfish development.
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Cite this article as:
Hu W.-F., Li D.W.-C., Liu S.-J., Liu Y.-Z., Yu M.-B., Luo L.-X., Liu X.-L., Wu M.-X., Wu K.-L., Woodward Z., Liu W.-B., Hu X.-H., Ji W.-K., Zhang X.-W., Nie L., Liu J., Chen H.-G., Tang X.-C., Liu F.-Y. and Yan Q., Protein Serine/Threonine Phosphotase-1 is Essential in Governing Normal Development of Vertebrate Eye, Current Molecular Medicine 2012; 12 (10) . https://dx.doi.org/10.2174/156652412803833535
DOI https://dx.doi.org/10.2174/156652412803833535 |
Print ISSN 1566-5240 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5666 |
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