Protein Serine/Threonine Phosphotase-2A is Differentially Expressed and Regulates Eye Development in Vertebrates

J.      Liu; D.   W.-C.   Li; S.-J.      Liu; Y.      Liu; L.      Wang; T.-T.      Li; M.      Yi; L.      Li; Z.-X.      Huang; W.-F.      Hu; W.-B.      Liu; C.      Zhang; M.      Tao; W.      Duan; S.-S.      Hui; L.      Nie; M.-X.      Deng; X.-W.      Zhang; X.-H.      Hu

doi:10.2174/15665240113139990061

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.

Keywords: Apoptosis, differentiation, eye development, lens, PP-2A, PP-2Acα/β, protein phosphatases, retina.