Interphase phosphorylation of lamin A

A1 Journal article (refereed)


Internal Authors/Editors


Publication Details

List of Authors: Kochin V, Shimi T, Torvaldson E, Adam SA, Goldman A, Pack CG, Melo-Cardenas J, Imanishi SY, Goldman RD, Eriksson JE
Publisher: The Company of Biologists Ltd
Publication year: 2014
Journal: Journal of Cell Science
Journal acronym: J Cell Sci
Volume number: 127
Start page: 2683
End page: 2696
ISSN: 1477-9137
eISSN: 1477-9137


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.

Last updated on 2019-22-09 at 02:45