Torsin ATPases influence chromatin interaction of the Torsin regulator LAP1.
The inner nuclear membrane is functionalized by diverse transmembrane proteins that associate with nuclear lamins and/or chromatin. When cells enter mitosis, membrane-chromatin contacts must be broken to allow for proper chromosome segregation; yet how this occurs remains ill-understood. Unexpectedly, we observed that an imbalance in the levels of the lamina-associated polypeptide 1 (LAP1), an activator of ER-resident Torsin AAA+-ATPases, causes a failure in membrane removal from mitotic chromatin, accompanied by chromosome segregation errors and changes in post-mitotic nuclear morphology. These defects are dependent on a hitherto unknown chromatin-binding region of LAP1 that we have delineated. LAP1-induced NE abnormalities are efficiently suppressed by expression of wild-type but not ATPase-deficient Torsins. Furthermore, a dominant-negative Torsin induces chromosome segregation defects in a LAP1-dependent manner. These results indicate that association of LAP1 with chromatin in the nucleus can be modulated by Torsins in the perinuclear space, shedding new light on the LAP1-Torsin interplay.
['Luithle|Naemi|N|', 'de Bos|Jelmi Uit|JU|0000-0002-8807-3284', 'Hovius|Ruud|R|0000-0001-9258-6587', 'Maslennikova|Daria|D|', 'Lewis|Renard Tm|RT|', 'Ungricht|Rosemarie|R|', 'Fierz|Beat|B|', 'Kutay|Ulrike|U|0000-0002-8257-7465']
D000251:Adenosine Triphosphatases D002352:Carrier Proteins D045744:Cell Line, Tumor D002843:Chromatin D020090:Chromosome Segregation D055786:Gene Knockout Techniques D045325:HCT116 Cells D050883:HSC70 Heat-Shock Proteins D006367:HeLa Cells D056945:Hep G2 Cells D006801:Humans D008938:Mitosis D018832:Molecular Chaperones D009685:Nuclear Envelope
Torsins LAP1 inner nuclear membrane mitosis chromosome segregation cell biology human nuclear envelope