Pradeep G Kumar
Rajiv Gandhi Centre for Biotechnology, India
Title: Autoimmune regulator (AIRE) regulates the expression of several nucleic acid binding and cytoskeletal proteins in spermatogonia
Biography
Biography: Pradeep G Kumar
Abstract
Autoimmune Regulator (AIRE) is a gene associated with Autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED). AIRE is expressed heavily in the thymic epithelial cells and is involved in maintaining self tolerance through regulating the expression of tissue specific antigens. Testis is the most predominant extra-thymic location where a heavy expression of AIRE is reported. Homozygous Aire-deficient male mice were infertile, possibly due to impaired spermatogenesis, deregulated germ cell apoptosis or autoimmunity. We report that AIRE is expressed in the testis of neonatal, adolescent and adult mice. AIRE expression was detected in GFRα+ (spermatogonia), GFRα-/SCP3+ (meiotic) and GFRα-/PGK2+ (post-meiotic) germ cells in mouse testis. GC1-spg, a germ cell derived cell line, did not express AIRE. Retinoic acid induced AIRE expression in GC1-spg cells. Ectopic expression of AIRE in GC1-spg cells using label-free LC-MS/MS identified a total of 371 proteins which were differentially expressed. 100 proteins were up regulated and 271 proteins were down regulated. Data are available via ProteomeXchange with identifier PXD002511. Functional analysis of the differentially expressed proteins showed increased levels of various nucleic acid binding proteins and transcription factors and a decreased level of various cytoskeletal and structural proteins in the Aire over expressing cells as compared to the empty vector transfected controls. The transcripts of a select set of the upregulated proteins were also elevated. However, there was no corresponding decrease in the mRNA levels of the downregulated set of proteins. Molecular function network analysis indicated that AIRE influenced gene expression in GC1-spg cells by acting at multiple levels including transcription, translation, RNA processing, protein transport, protein localization and protein degradation, thus setting the foundation in understanding the functional role of AIRE in germ cell biology.