Please use this identifier to cite or link to this item: http://hdl.handle.net/2381/31583
Title: Mitotic phosphorylation of SUN1 loosens its connection with the nuclear lamina while the LINC complex remains intact.
Authors: Patel, Jennifer T.
Bottrill, Andrew
Prosser, Suzanna L.
Jayaraman, Sangeetha
Straatman, Kees
Fry, Andrew M.
Shackleton, Sue
First Published: 26-Aug-2014
Publisher: Taylor & Francis, Landes Bioscience
Citation: Jennifer T Patel, Andrew Bottrill, Suzanna L Prosser, Sangeetha Jayaraman, Kees Straatman, Andrew M Fry & Sue Shackleton (2014) Mitotic phosphorylation of SUN1 loosens its connection with the nuclear lamina while the LINC complex remains intact, Nucleus, 5:5, 462-473
Abstract: At the onset mitosis in higher eukaryotes, the nuclear envelope (NE) undergoes dramatic deconstruction to allow separation of duplicated chromosomes. Studies have shown that during this process of nuclear envelope breakdown (NEBD), the extensive protein networks of the nuclear lamina are disassembled through phosphorylation of lamins and several inner nuclear membrane (INM) proteins. The LINC complex, composed of SUN and nesprin proteins, is involved in multiple interactions at the NE and plays vital roles in nuclear and cellular mechanics by connecting the nucleus to the cytoskeleton. Here, we show that SUN1, located in the INM, undergoes mitosis-specific phosphorylation on at least 3 sites within its nucleoplasmic N-terminus. We further identify Cdk1 as the kinase responsible for serine 48 and 333 phosphorylation, while serine 138 is phosphorylated by Plk1. In mitotic cells, SUN1 loses its interaction with N-terminal domain binding partners lamin A/C, emerin, and short nesprin-2 isoforms. Furthermore, a triple phosphomimetic SUN1 mutant displays increased solubility and reduced retention at the NE. In contrast, the central LINC complex interaction between the SUN1 C-terminus and the KASH domain of nesprin-2 is maintained during mitosis. Together, these data support a model whereby mitotic phosphorylation of SUN1 disrupts interactions with nucleoplasmic binding partners, promoting disassembly of the nuclear lamina and, potentially, its chromatin interactions. At the same time, our data add to an emerging picture that the core LINC complex plays an active role in NEBD.
DOI Link: 10.4161/nucl.36232
ISSN: 1949-1034
eISSN: 1949-1042
Links: http://www.tandfonline.com/doi/abs/10.4161/nucl.36232
http://hdl.handle.net/2381/31583
Version: Post-print
Status: Peer-reviewed
Type: Journal Article
Rights: Archived with reference to SHERPA/RoMEO and publisher website. This is an Accepted Manuscript of an article published by Taylor & Francis in Nucleus on 2014-08-26, available online: http://www.tandfonline.com/doi/abs/10.4161/nucl.36232
Description: PMCID: PMC4164488
Appears in Collections:Published Articles, Dept. of Biochemistry

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