Interphase phosphorylation of lamin A

Vitaly Kochin, T Shimi, Elin Torvaldson, SA Adam, A Goldman, CG Pack, J Melo-Cardenas, Susumu Imanishi, RD Goldman, John Eriksson

    Research output: Contribution to journalArticleScientificpeer-review

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    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 high-turnover sites. We examined the roles of these latter sites by site-directed 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 languageUndefined/Unknown
    Pages (from-to)2683–2696
    JournalJournal of Cell Science
    Volume127
    DOIs
    Publication statusPublished - 2014
    MoE publication typeA1 Journal article-refereed

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