Lamin A phosphorylation in interphase Free

Nuclear lamins are a main component of the nuclear lamina and, thus, essential for the structure and integrity of the nucleus. Consequently, mutations in lamins affect lamin organization and assembly and give rise to the so-called laminopathies with broad phenotypes including premature aging syndromes. However, only little is known regarding the regulation of lamin assembly and structure within the nucleus. As lamin phosphorylation has been shown to be important for regulating its disassembly and reassembly during mitosis, John Eriksson and colleagues reasoned that it might also have a role during interphase and, on page 2683, set out to identify the bona fide in vivo phosphorylation sites in lamin A by mass spectroscopy. They find 20 interphase phosphorylation sites restricted to three different regions. Among these, eight are high-turnover sites that the authors characterise further. Interestingly, the two main mitotic phosphorylation sites of lamin A, Ser22 and Ser392, are also important interphase sites, and mutation of these sites has profound effects on lamin organisation and dynamics by redistributing lamin A to the nucleoplasm. Furthermore, another high-turnover site, Ser628, is located within a region of lamin A that is missing in progerin – the permanently farnesylated and truncated dominant-negative form of lamin A that is present in the premature aging disease Hutchinson-Gilford progeria syndrome – suggesting that loss of phosphorylation contributes to the disease mechanism. On the basis of these results, the authors propose a lamin phosphorylation code, through which phosphorylation at different sites governs its distribution and organisation and, thus, function.