Interphase phosphorylation of lamin A

Vitaly Kochin, Takeshi Shimi, Elin Torvaldson, Stephen A. Adam, Anne Goldman, Chan Gi Pack, Johanna Melo-Cardenas, Susumu Y. Imanishi, Robert D. Goldman, John E. Eriksson*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

81 Scopus citations

Abstract

Nuclear lamins form the major structural elements that comprise the nuclear lamina. Loss of nuclear structural integrity has been implicated as a key factor in the lamin A/C gene mutations that cause laminopathies, whereas the normal regulation of lamin A assembly and organization in interphase cells is still undefined. We assumed phosphorylation to be a major determinant, identifying 20 prime interphase phosphorylation sites, of which eight were highturnover sites. We examined the roles of these latter sites by sitedirected mutagenesis, followed by detailed microscopic analysis - including fluorescence recovery after photobleaching, fluorescence correlation spectroscopy and nuclear extraction techniques. The results reveal three phosphorylation regions, each with dominant sites, together controlling lamin A structure and dynamics. Interestingly, two of these interphase sites are hyper-phosphorylated in mitotic cells and one of these sites is within the sequence that is missing in progerin of the Hutchinson-Gilford progeria syndrome. We present a model where different phosphorylation combinations yield markedly different effects on the assembly, subunit turnover and the mobility of lamin A between, and within, the lamina, the nucleoplasm and the cytoplasm of interphase cells.

Original languageEnglish (US)
Pages (from-to)2683-2696
Number of pages14
JournalJournal of cell science
Volume127
Issue number12
DOIs
StatePublished - 2014

Keywords

  • Intermediate filament
  • Lamin A
  • Phosphorylation
  • Sequestration
  • Signaling

ASJC Scopus subject areas

  • Cell Biology

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