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Publication : PTBP1 mediates Sertoli cell actin cytoskeleton organization by regulating alternative splicing of actin regulators.

First Author  Wang Y Year  2024
Journal  Nucleic Acids Res PubMed ID  39373517
Mgi Jnum  J:357529 Mgi Id  MGI:7764128
Doi  10.1093/nar/gkae862 Citation  Wang Y, et al. (2024) PTBP1 mediates Sertoli cell actin cytoskeleton organization by regulating alternative splicing of actin regulators. Nucleic Acids Res
abstractText  Spermatogenesis is a biological process within the testis that produces haploid spermatozoa for the continuity of species. Sertoli cells are somatic cells in the seminiferous epithelium that orchestrate spermatogenesis. Cyclic reorganization of the Sertoli cell actin cytoskeleton is vital for spermatogenesis, but the underlying mechanism remains largely unclear. Here, we report that the RNA-binding protein PTBP1 controls Sertoli cell actin cytoskeleton reorganization by programming alternative splicing of actin cytoskeleton regulators. This splicing control enables ectoplasmic specializations, the actin-based adhesion junctions, to maintain the blood-testis barrier and support spermatid transport and transformation. Particularly, we show that PTBP1 promotes actin bundle formation by repressing the inclusion of exon 14 of Tnik, a kinase present at the ectoplasmic specialization. Our results thus reveal a novel mechanism wherein Sertoli cell actin cytoskeleton dynamics are controlled post-transcriptionally by utilizing functionally distinct isoforms of actin regulatory proteins, and PTBP1 is a critical regulatory factor in generating such isoforms.
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