The Role Of PP2A In Mouse Rod Cells

Photoreceptor cell death is the proximal cause of blindness in many retinal degenerative disorders.The protein phosphatase 2A?PP2A?has a key role in photoreceptor development and function maintenance.Serine/threonine protein phosphatases control the dephosphorylation of a variety of proteins.PP2A is one of the most abundant serine/threonine phosphatases,with a critical role in embryonic development and human disease.PP2A is a heterotrimer consisting of an A structural subunit,a B regulatory and a C catalytic subunit,and the B subunit gives the complex substrate specificity.There are two isoforms?and?of A and C subunits in eukaryotes.The regulatory B subunits play key roles in controlling PP2A substrate specificity,cellular localization,and enzymatic activity.Each family of B subunits contains several isoforms that can bind the AC dimer in a mutually exclusive manner.The?form of PP2A catalytic subunit was encoded by mouse gene ppp2ca.Conventional knockout of ppp2ca allele leads to embryonic lethality in mice.To explore the changes of retina structure and function and molecular mechanisms in mouse conditional deleted ppp2ca in rod cells,we set up ppp2ca conditional knockout mice models by Rho-Cre mice with ppp2ca^flox/flox mice.Exon 2 of Ppp2ca was knocked out in a spatial-specific manner in rod photoreceptor cells.Retcam,OCT,HE,f ERG,Immunohistochemistry,western blot,and many other methods were used.The effect of Ppp2ca disruption was characterized on retinal apoptosis,function,and morphology.Electroretinogram recordings under scotopic conditions showed severe attenuation of the a-wave,confirming the degeneration of photoreceptors.The outer segment of rod was destroyed,and the retina became thinner.The Fundus of 6months c KO mouse was similar to that of retinitis pigmentosa by Retcam.Protein levels of PP2AC,rhodopsin,opsin and Akt decrease significantly in knockout mice.In summary,our study proved the key function of PP2A in adult mice photoreceptor function.By phenotyping the rod specific ppp2ca null mice,we found knockout mice photoreceptors became degeneration,and the regulation of the Akt pathway is disturbed in PP2A knockout mice.