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Samp1, a RanGTP binding transmembrane protein in the inner nuclear membrane
Stockholm University, Faculty of Science, Department of Neurochemistry.
Stockholm University, Faculty of Science, Department of Neurochemistry.
Stockholm University, Faculty of Science, Department of Neurochemistry.
Stockholm University, Faculty of Science, Department of Neurochemistry.
Number of Authors: 4
2016 (English)In: Nucleus, ISSN 1949-1034, E-ISSN 1949-1042, Vol. 7, no 4, 415-423 p.Article in journal (Refereed) Published
Abstract [en]

Samp1 is a transmembrane protein of the inner nuclear membrane (INM), which interacts with the nuclear lamina and the Linker of Nucleoskeleton and Cytoskeleton (LINC) complex in interphase and during mitosis, it localizes to the mitotic spindle. Samp1 was recently found to coprecipitate a protein complex containing Ran, a GTPase with fundamental regulatory functions both in interphase and in mitosis. To investigate the interaction between Samp1 and Ran in further detail, we have designed and expressed recombinant fusion proteins of the Chaetomium thermophilum homolog of Samp1 (Ct. Samp1) and human Ran. Pulldown experiments show that Samp1 binds directly to Ran and that Samp1 binds better to RanGTP compared to RanGDP. Samp1 also preferred RanGTP over RanGDP in living tsBN2 cells. We also show that the Ran binding domain is located between amino acids 75-135 in the nucleoplasmically exposed N-terminal tail of Samp1. This domain is unique for Samp1, without homology in any other proteins in fungi or metazoa. Samp1 is the first known transmembrane protein that binds to Ran and could provide a unique local binding site for RanGTP in the INM. Samp1 overexpression resulted in increased Ran concentrations in the nuclear periphery supporting this idea.

Place, publisher, year, edition, pages
2016. Vol. 7, no 4, 415-423 p.
Keyword [en]
EDMD, laminopathies, LINC complex, nucleus, nuclear membrane, Ran
National Category
Biological Sciences
Identifiers
URN: urn:nbn:se:su:diva-135087DOI: 10.1080/19491034.2016.1220465ISI: 000384442800010PubMedID: 27541860OAI: oai:DiVA.org:su-135087DiVA: diva2:1048983
Available from: 2016-11-23 Created: 2016-10-31 Last updated: 2017-04-19Bibliographically approved
In thesis
1. Multifaceted roles of the transmembrane nuclear envelope protein, Samp1
Open this publication in new window or tab >>Multifaceted roles of the transmembrane nuclear envelope protein, Samp1
2017 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

The eukaryotic nuclear envelope (NE), separates the nucleoplasm from cytoplasm and is made up of two concentric lipid membranes, the outer and the inner nuclear membranes (ONM and INM), the nuclear pore complexes (NPCs) and an underlying filamentous nuclear lamina. The INM contains hundreds of unique transmembrane proteins of which only a handful have been characterized. In this thesis, I aimed to understand the functional organization of proteins in the nuclear envelope and I focused on investigating the functions of a recently identified INM transmembrane protein, Samp1. We have developed a novel and robust approach, MCLIP, to identify specific protein-protein interactions taking place in live cells. Using MCLIP, we have shown that Samp1 interacts with proteins of the LINC complex, the nuclear lamina and components of the mitotic spindle. Samp1's specific interactions with a variety of binding partners, suggest that Samp1 plays important roles both in interphase and in mitosis.  We have also shown that Samp1 can provide a binding site at the INM for the GTPase Ran, a master regulator of protein interactions in interphase and in mitosis. Furthermore, we have also investigated the role of Samp1 in cell differentiation using two independent model systems. In human iPSCs, ectopic expression of Samp1 promoted differentiation despite pluripotent culture conditions. In C2C12 myoblast, depletion of Samp1 completely blocked differentiation into myotubes. The two studies complement each other and suggest that Samp1 has a strong differentiation promoting activity. Taken together, the findings in this thesis, give insights on the unexpected and unforeseen roles played by a transmembrane protein in different fundamental cellular process.

Place, publisher, year, edition, pages
Stockholm: Department of Neurochemistry, Stockholm University, 2017. 46 p.
Keyword
Nuclear envelope, transmembrane protein interaction studies, cell differentiation, stem cells, myopathies
National Category
Biochemistry and Molecular Biology Cell Biology Chemical Sciences
Research subject
Neurochemistry with Molecular Neurobiology
Identifiers
urn:nbn:se:su:diva-141816 (URN)978-91-7649-577-3 (ISBN)978-91-7649-578-0 (ISBN)
Public defence
2017-05-31, Magnélisalen, Kemiska övningslaboratoriet, Svante Arrhenius väg 16 B, Stockholm, 10:00 (English)
Opponent
Supervisors
Note

At the time of the doctoral defense, the following papers were unpublished and had a status as follows: Paper 3: Manuscript. Paper 4: Manuscript. Paper 5: Manuscript.

Available from: 2017-05-08 Created: 2017-04-19 Last updated: 2017-06-02Bibliographically approved

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