Hypertonic-induced lamin A/C synthesis and distribution to nucleoplasmic speckles is mediated by TonEBP/NFAT5 transcriptional activator.
Lamin A/C is the most studied nucleoskeletal constituent. Lamin A/C expression indicates cell differentiation and is also a structural component of nuclear speckles, which are involved in gene expression regulation. Hypertonicity has been reported to induce renal epithelial cell differentiation and expression of TonEBP (NFAT5), a transcriptional activator of hypertonicity-induced gene transcription. In this paper, we investigate the effect of hypertonicity on lamin A/C expression in MDCK cells and the involvement of TonEBP. Hypertonicity increased lamin A/C expression and its distribution to nucleoplasm with speckled pattern. Microscopy showed codistribution of TonEBP and lamin A/C in nucleoplasmic speckles, and immunoprecipitation demonstrated their interaction. TonEBP silencing caused lamin A/C redistribution from nucleoplasmic speckles to the nuclear rim, followed by lamin decrease, thus showing that hypertonicity induces lamin A/C speckles through a TonEBP-dependent mechanism. We suggest that lamin A/C speckles could serve TonEBP as scaffold thus favoring its role in hypertonicity.
Favale
Nicolás O
NO
Department of Biological Sciences, School of Pharmacy and Biochemistry, University of Buenos Aires, Junín 956, 1er piso, IQUIFIB-CONICET, Ciudad Autónoma de Buenos Aires (C1113AAD), Argentina.
Sterin Speziale
Norma B
NB
Fernández Tome
María C
MC
D000818:Animals; D002460:Cell Line; D022003:Cell Nucleus Structures / Q000187:drug effects* / Q000378:metabolism*; D004285:Dogs; D020868:Gene Silencing / Q000187:drug effects; D006982:Hypertonic Solutions / Q000494:pharmacology*; D047468:Immunoprecipitation; D034904:Lamin Type A / Q000096:biosynthesis* / Q000378:metabolism*; D050778:NFATC Transcription Factors / Q000378:metabolism*; D021381:Protein Transport / Q000187:drug effects; D015534:Trans-Activators / Q000378:metabolism*
D006982:Hypertonic Solutions; D034904:Lamin Type A; D050778:NFATC Transcription Factors; D015534:Trans-Activators