| First Author | Vikhe Patil K | Year | 2023 |
| Journal | Philos Trans R Soc Lond B Biol Sci | Volume | 378 |
| Issue | 1890 | Pages | 20220451 |
| PubMed ID | 37778375 | Mgi Jnum | J:371348 |
| Mgi Id | MGI:7778603 | Doi | 10.1098/rstb.2022.0451 |
| Citation | Vikhe Patil K, et al. (2023) Co-expression of PADI isoforms during progenitor differentiation enables functional diversity. Philos Trans R Soc Lond B Biol Sci 378(1890):20220451 |
| abstractText | Protein isoforms, generated through alternative splicing or promoter usage, contribute to tissue function. Here, we characterize the expression of predicted Padi3alpha and Padi3beta isoforms in hair follicles and describe expression of Padi2beta, a hitherto unknown PADI2 isoform, in the oligodendrocyte lineage. Padi2beta transcription is initiated from a downstream intronic promoter, generating an N-terminally truncated, unstable, PADI2beta. By contrast to the established role of the canonical PADI2 (PADI2alpha) (Falcao et al. 2019 Cell Rep. 27, 1090-1102.e10. (doi:10.1016/j.celrep.2019.03.108)), PADI2beta inhibits oligodendrocyte differentiation, suggesting that PADI2 isoforms exert opposing effects on oligodendrocyte lineage progression. We localize Padi3alpha and Padi3beta to developing hair follicles and find that both transcripts are expressed at low levels in progenitor cells, only to increase in expression concomitant with differentiation. When expressed in vitro, PADI3alpha and PADI3beta are enriched in the cytoplasm and precipitate together. Whereas PADI3beta protein stability is low and PADI3beta fails to induce protein citrullination, we find that the enzymatic activity and protein stability of PADI3alpha is reduced in the presence of PADI3beta. We propose that PADI3beta modulates PADI3alpha activity by direct binding and heterodimer formation. Here, we establish expression and function of Padi2 and Padi3 isoforms, expanding on the mechanisms in place to regulate citrullination in complex tissues. This article is part of the Theo Murphy meeting issue 'The virtues and vices of protein citrullination'. |
