title: Phosphomimetic mutation of the mitotically phosphorylated serine 1880 compromises the interaction of the transmembrane nucleoporin gp210 with the nuclear pore complex.
abstract: The nuclear pore complexes (NPCs) reversibly disassemble and reassemble during mitosis. Disassembly of the NPC is accompanied by phosphorylation of many nucleoporins although the function of this is not clear. It was previously shown that in the transmembrane nucleoporin gp210 a single serine residue at position 1880 is specifically phosphorylated during mitosis. Using amino acid substitution combined with live cell imaging, time-lapse microscopy and FRAP, we investigated the role of serine 1880 in binding of gp210 to the NPC in vivo. An alanine substitution mutant (S1880A) was significantly more dynamic at the NPC compared to the wild-type protein, suggesting that serine 1880 is important for binding of gp210 to the NPC. Moreover a glutamate substitution (S1880E) closely mimicking phosphorylated serine specifically interfered with incorporation of gp210 into the NPC and compromised its post-mitotic recruitment to the nuclear envelope of daughter nuclei. Our findings are consistent with the idea that mitotic phosphorylation acts to dissociate gp210 from the structural elements of the NPC.
authors.affiliation: Life Sciences, Södertörns University College, Huddinge, Sweden.
authors.forename: Evgeny A
authors.initials: EA
authors.lastname: Onischenko
authors.forename: Ellinor
authors.initials: E
authors.lastname: Crafoord
authors.forename: Einar
authors.initials: E
authors.lastname: Hallberg
mesh_terms: D019943:Amino Acid Substitution; D000818:Animals; D036681:Fluorescence Recovery After Photobleaching; D016193:G1 Phase; D051379:Mice; D008938:Mitosis; D009154:Mutation / Q000235:genetics*; D041681:NIH 3T3 Cells; D009685:Nuclear Envelope / Q000378:metabolism; D022022:Nuclear Pore / Q000378:metabolism*; D028861:Nuclear Pore Complex Proteins / Q000378:metabolism*; D010766:Phosphorylation; D010768:Phosphoserine / Q000378:metabolism*; D011485:Protein Binding; D051381:Rats; D013329:Structure-Activity Relationship
chemical_list: D028861:Nuclear Pore Complex Proteins; C522336:Nup210 protein, rat; D010768:Phosphoserine