| Nuclear import of exogenous FGF1 requires the ER-protein LRRC59 and the importins Kpnα1 and Kpnβ1. | |
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MedLine Citation:
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PMID: 22321063 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
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FGF1 taken up by cells into endocytic vesicles can be translocated across vesicular membranes into the cytosol and the nucleus where it has a growth regulatory activity. Previously, LRRC59 was identified as an intracellular binding partner of FGF1, but its biological role remained unknown. Here we show that LRRC59 is strictly required for nuclear import of exogenous FGF1. siRNA-mediated depletion of LRRC59 did not inhibit translocation of FGF1 into cytosol, but blocked the nuclear import of FGF1. We found that also a NLS in FGF1, Ran GTPase, karyopherin-α1 (Kpnα1), and karyopherin-β1 (Kpnβ1) were required for nuclear import of FGF1. Nuclear import of exogenous FGF2, which depends on CEP57/Translokin, was independent of LRRC59, but was dependent on Kpnα1 and Kpnβ1, while the nuclear import of FGF1 was independent of CEP57. LRRC59 is a membrane anchored protein that localizes to the ER and the nuclear envelope (NE). We found that LRRC59 possesses NLS-like sequences in its cytosolic part that can mediate nuclear import of soluble LRRC59 variants, and that the localization of LRRC59 to the NE depends on Kpnβ1. We propose that LRRC59 facilitates transport of cytosolic FGF1 through nuclear pores by interaction with karyopherins and movement of LRRC59 along the ER and NE membranes. |
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Authors:
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Yan Zhen; Vigdis Sørensen; Camilla Skiple Skjerpen; Ellen Margrethe Haugsten; Yixin Jin; Sebastien Wälchli; Sjur Olsnes; Antoni Wiedlocha |
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Publication Detail:
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Type: JOURNAL ARTICLE Date: 2012-2-9 |
Journal Detail:
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Title: Traffic (Copenhagen, Denmark) Volume: - ISSN: 1600-0854 ISO Abbreviation: - Publication Date: 2012 Feb |
Date Detail:
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Created Date: 2012-2-10 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 100939340 Medline TA: Traffic Country: - |
Other Details:
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Languages: ENG Pagination: - Citation Subset: - |
Copyright Information:
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© 2012 John Wiley & Sons A/S. |
Affiliation:
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Department of Biochemistry, Institute for Cancer Research, The Norwegian Radium Hospital, Montebello, 0310 Oslo, Norway. Centre for Cancer Biomedicine, Faculty of Medicine, University of Oslo, Norway. Department of Immunology, Institute for Cancer Research, The Norwegian Radium Hospital, Montebello, 0310 Oslo, Norway. |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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