title: Possible role of HIWI2 in modulating tight junction proteins in retinal pigment epithelial cells through Akt signaling pathway.
abstract: PIWI subfamily of proteins is shown to be primarily expressed in germline cells. They maintain the genomic integrity by silencing the transposable elements. Although the role of PIWI proteins in germ cells has been documented, their presence and function in somatic cells remains unclear. Intriguingly, we detected all four members of PIWI-like proteins in human ocular tissues and somatic cell lines. When HIWI2 was knocked down in retinal pigment epithelial cells, the typical honeycomb morphology was affected. Further analysis showed that the expression of tight junction (TJ) proteins, CLDN1, and TJP1 were altered in HIWI2 knockdown. Moreover, confocal imaging revealed disrupted TJP1 assembly at the TJ. Previous studies report the role of GSK3β in regulating TJ proteins. Accordingly, phospho-kinase proteome profiler array indicated increased phosphorylation of Akt and GSK3α/β in HIWI2 knockdown, suggesting that HIWI2 might affect TJ proteins through Akt-GSK3α/β signaling axis. Moreover, treating the HIWI2 knockdown cells with wortmannin increased the levels of TJP1 and CLDN1. Taken together, our study demonstrates the presence of PIWI-like proteins in somatic cells and the possible role of HIWI2 in preserving the functional integrity of epithelial cells probably by modulating the phosphorylation status of Akt.
authors.affiliation: RS Mehta Jain Department of Biochemistry and Cell Biology, Vision Research Foundation, Chennai, India.|School of Chemical and Biotechnology, SASTRA University, Thanjavur, India.
authors.forename: Suganya
authors.initials: S
authors.lastname: Sivagurunathan
authors.affiliation: RS Mehta Jain Department of Biochemistry and Cell Biology, Vision Research Foundation, Chennai, India.|School of Chemical and Biotechnology, SASTRA University, Thanjavur, India.
authors.forename: Karthikka
authors.initials: K
authors.lastname: Palanisamy
authors.affiliation: SN ONGC Department of Genetics and Molecular Biology, Vision Research Foundation, Chennai, India.
authors.forename: Jayamuruga Pandian
authors.initials: JP
authors.lastname: Arunachalam
authors.affiliation: RS Mehta Jain Department of Biochemistry and Cell Biology, Vision Research Foundation, Chennai, India. csubbulakshmi@gmail.com.|Department of Biochemistry and Molecular Biology, Pondicherry University, Pondicherry, India. csubbulakshmi@gmail.com.
authors.forename: Subbulakshmi
authors.initials: S
authors.lastname: Chidambaram
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D002478:Cells, Cultured; D062445:Claudin-1 / Q000096:biosynthesis / Q000235:genetics; D005260:Female; D055785:Gene Knockdown Techniques; D000071679:Glycogen Synthase Kinase 3 beta / Q000096:biosynthesis / Q000235:genetics; D006801:Humans; D008297:Male; D008875:Middle Aged; D011506:Proteins / Q000235:genetics / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics / Q000378:metabolism*; D016601:RNA-Binding Proteins; D055213:Retinal Pigment Epithelium / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology*; D019108:Tight Junctions / Q000235:genetics / Q000378:metabolism*; D062826:Zonula Occludens-1 Protein / Q000096:biosynthesis / Q000235:genetics
chemical_list: C568108:CLDN1 protein, human; D062445:Claudin-1; C556795:PIWIL4 protein, human; D011506:Proteins; D016601:RNA-Binding Proteins; C569042:TJP1 protein, human; D062826:Zonula Occludens-1 Protein; C000605506:GSK3B protein, human; D000071679:Glycogen Synthase Kinase 3 beta; D051057:Proto-Oncogene Proteins c-akt
keywords: Akt pathway; HIWI2; PIWIL proteins; Retinal pigment epithelium; Tight junctions