Lamin A/C phosphorylation at serine 22 is a conserved heat shock response to regulate nuclear adaptation during stress

Laura Virtanen, Emilia Holm, Mona Halme, Gun West, Fanny Lindholm, Josef Gullmets, Juho Irjala, Tiina Heliö, Artur Padzik, Annika Meinander, John E Eriksson, Pekka Taimen

Forskningsoutput: TidskriftsbidragArtikelVetenskapligPeer review

Sammanfattning

The heat shock (HS) response is crucial for cell survival in harmful environments. Nuclear lamin A/C (LA/C), encoded by LMNA gene, contributes towards altered gene expression during HS, but the underlying mechanisms are poorly understood. Here we show that upon HS, LA/C is reversibly phosphorylated at Ser22 in concert with HSF1 activation in human cells, mouse cells and D. melanogaster in vivo. Consequently, the phosphorylation facilitated nucleoplasmic localization of LA/C and nuclear sphericity in response to HS. Interestingly, LA/C knock-out cells showed deformed nuclei after HS and were rescued by ectopic expression of wild-type LA, but not by a phosphomimetic (S22D) LA mutant. Furthermore, HS triggered concurrent downregulation of lamina-associated protein 2α (Lap2α) in wild-type LA/C expressing cells but a similar response was perturbed in LA/C knock-out cells and in LMNA mutant patient fibroblasts which showed impaired cell cycle arrest under HS and compromised survival at the recovery. Taken together, our results suggest that the altered phosphorylation stoichiometry of LA/C provides an evolutionary conserved mechanism to regulate lamina structure and serve nuclear adaptation and cell survival during HS.

OriginalspråkEngelska
TidskriftJournal of Cell Science
DOI
StatusE-pub före tryck - 25 jan. 2023
MoE-publikationstypA1 Tidskriftsartikel-refererad

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