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Recombinant α- β- and γ-Synucleins Stimulate Protein Phosphatase 2A Catalytic Subunit Activity in Cell Free Assays
Published on: August 13, 2017
Protein serine/threonine Phosphotase-2A is differentially expressed and regulates eye development in vertebrates
1Key Laboratory of Protein Chemistry and Development Biology of National Education Department, College of Life Science, Hunan Normal University, Changsha, China.
Abstract:
Protein serine/threonine phosphatase-2A (PP-2A) is one of the key enzymes responsible for dephosphorylation in vertebrates. PP-2A-mediated dephosphorylation participates in many different biological processes including cell proliferation, differentiation, transformation, apoptosis, autophage and senescence. However, whether PP-2A directly controls animal development remains to be explored. Here, we present direct evidence to show that PP-2A displays important functions in regulating eye development of vertebrates. Using goldfish as a model system, we have demonstrated the following novel information. First, inhibition of PP-2A activity leads to significant death of the treated embryos, which is derived from blastomere apoptosis associated with enhanced phosphorylation of Bcl-XL at Ser-62, and the survived embryos displayed severe phenotype in the eye. Second, knockdown of PP-2A with morpholino oligomers leads to significant death of the injected embryos. The survived embryos from PP-2A knockdown displayed clear retardation in lens differentiation. Finally, overexpression of each catalytic subunit of PP-2A also causes death of majority of the injected embryos and leads to absence of goldfish eye lens or severely disturbed differentiation. Together, our results provide direct evidence that protein phosphatase-2A is important for normal eye development in goldfish.
Insights
Protein phosphatase-2A (PP-2A) is crucial for vertebrate eye development. Inhibiting PP-2A causes embryo death and severe eye defects, while its knockdown or overexpression disrupts lens differentiation.
Area of Science:
- Developmental Biology
- Molecular Biology
- Cell Biology
Background:
- Protein serine/threonine phosphatase-2A (PP-2A) is a key enzyme regulating dephosphorylation.
- PP-2A participates in critical cellular processes like proliferation, apoptosis, and differentiation.
- Its direct role in vertebrate animal development, particularly eye development, is not well understood.
Purpose of the Study:
- To investigate the function of PP-2A in vertebrate eye development.
- To provide direct evidence for PP-2A's role in regulating eye formation and differentiation.
Main Methods:
- Utilized goldfish as a model organism.
- Inhibited PP-2A activity using chemical inhibitors.
- Knocked down PP-2A expression using morpholino oligomers.
- Overexpressed catalytic subunits of PP-2A.
Main Results:
- PP-2A inhibition led to embryo death via apoptosis and severe eye phenotypes in survivors.
- PP-2A knockdown caused embryo mortality and significant lens differentiation retardation.
- Overexpression of PP-2A catalytic subunits resulted in embryo death and absence or malformation of the eye lens.
Conclusions:
- Protein phosphatase-2A plays a critical and essential role in normal goldfish eye development.
- PP-2A is vital for preventing blastomere apoptosis and ensuring proper lens differentiation during eye formation.
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