Change search
ReferencesLink to record
Permanent link

Direct link
Phosphomimetic mutation of the mitotically phosphorylated serine 1880 compromises the interaction of the transmembrane nucleoporin gp210 with the nuclear pore complex
Södertörn University, School of Life Sciences. Karolinska Institute.
Södertörn University, School of Life Sciences. Karolinska Institute.
Södertörn University, School of Life Sciences.
2007 (English)In: Experimental Cell Research, ISSN 0014-4827, E-ISSN 1090-2422, Vol. 313, no 12, 2744-2751 p.Article in journal (Refereed) Published
Abstract [en]

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 subtitutions 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.

Place, publisher, year, edition, pages
2007. Vol. 313, no 12, 2744-2751 p.
National Category
Cancer and Oncology Cell Biology
URN: urn:nbn:se:sh:diva-14217DOI: 10.1016/j.yexcr.2007.05.011ISI: 000248112300019PubMedID: 17559836ScopusID: 2-s2.0-34250885134OAI: diva2:467857

Som manuskript i avhandling. As manuscript in dissertation with title:

Mitotic phosphorylation regulates binding of gp210 to the nuclear pore complex

Available from: 2011-12-20 Created: 2011-12-19 Last updated: 2017-02-06Bibliographically approved
In thesis
1. Disassembly and reassembly of the nuclear pore complex
Open this publication in new window or tab >>Disassembly and reassembly of the nuclear pore complex
2006 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

The nuclear pore complexes (NPCs) are multiprotein communicative channels spanning the nuclear envelope. In higher eukaryotes NPCs reversibly disassemble during mitosis into distinct nucleoporin subcomplexes. Some cell types (e.g. oocytes and early embryonic cells) also contain mimics of NPCs of unknown function, which are located in cytoplasmic membranes. They are termed annulate lamellae pore complexes (ALPC). This study was aimed at understanding the process of mitotic disassembly and reassembly of the NPC and at elucidating the function of ALPCs. Using syncytial Drosophila embryos as a model we have tested the proposed function of ALPCs as a storage compartment for nucleoporins fueling assembly of new NPCs in rapidly proliferating cells. Surprisingly, we found that ALPCs are not depleted during assembly of new NPCs and that they represent only a minor fraction of the total embryonic nucleoporins while the major fraction is persistently soluble. We conclude that in Drosophila, ALPCs play only a minor role as a storage compartment for nucleoporins. We developed a novel in vivo model system based on syncytial Drosophila embryos to study mitotic disassembly/reassembly of the NPC. We found that the major mitotic kinase Cdk1 is the key regulator of both NPC and ALPC disassembly/reassembly in vivo and that Cdk1 activity is able to phosphorylate and solubilize nucleoporins in vitro. We also found that phosphatase activity, sensitive to okadaic acid (OA), is required for reassembly of both NPCs and ALPCs in vivo. Additionally, we showed that the Ran GTPase system, that drives active nucleocytoplasmic transport during intephase, is selectively required for post-mitotic reassembly of NPCs but not ALPCs in vivo. Our findings suggest that in live cells NPC assembly is regulated by a dynamic equilibrium between kinase (Cdk1) and phospahatase (sensitive to OA) activity and that it is spatially coordinated by the Ran GTPase system. Finally. using the nucleoporin gp210 as a model. we have tested a role of mitotic phosphorylation of nucleoporins in disassembly of the NPC. We present evidence that a single mitotic phosphorylation of gp210 weakens its binding to the NPC and interferes with its postmitotic recruitment to the newly formed NE. These findings represent the first direct evidence that mitotic nucleoporin phosphorylation functions in disassembly of the NPC.

Place, publisher, year, edition, pages
Stockholm: Karolinska instiutet, 2006. 65 p.
National Category
Biological Sciences
urn:nbn:se:sh:diva-31961 (URN)91-7140-929-7 (ISBN)
Public defence
2006-10-13, MA648, Alfred Nobels allé 7, Huddinge, 09:00 (English)
Available from: 2017-02-06 Created: 2017-02-06 Last updated: 2017-02-06Bibliographically approved

Open Access in DiVA

No full text

Other links

Publisher's full textPubMedScopus

Search in DiVA

By author/editor
Onischenko, Evgeny A.Crafoord, EllinorHallberg, Einar
By organisation
School of Life Sciences
In the same journal
Experimental Cell Research
Cancer and OncologyCell Biology

Search outside of DiVA

GoogleGoogle Scholar

Altmetric score

Total: 57 hits
ReferencesLink to record
Permanent link

Direct link