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Nuclear Import of Exogenous FGF 1 Requires the ER ‐Protein LRRC 59 and the Importins Kpn α1 and Kpn β1
Author(s) -
Zhen Yan,
Sørensen Vigdis,
Skjerpen Camilla S.,
Haugsten Ellen M.,
Jin Yixin,
Wälchli Sebastien,
Olsnes Sjur,
Wiedlocha Antoni
Publication year - 2012
Publication title -
traffic
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.677
H-Index - 130
eISSN - 1600-0854
pISSN - 1398-9219
DOI - 10.1111/j.1600-0854.2012.01341.x
Subject(s) - biology , microbiology and biotechnology , cytosol , endoplasmic reticulum , fgf1 , nuclear transport , nuclear export signal , nuclear localization sequence , importin , nuclear pore , cell nucleus , fibroblast growth factor , biochemistry , fibroblast growth factor receptor , nucleus , receptor , enzyme
Fibroblast growth factor 1 ( FGF 1) 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, leucine‐rich repeat containing 59 ( LRRC 59) was identified as an intracellular binding partner of FGF 1, but its biological role remained unknown. Here, we show that LRRC 59 is strictly required for nuclear import of exogenous FGF 1. siRNA ‐mediated depletion of LRRC 59 did not inhibit the translocation of FGF 1 into cytosol, but blocked the nuclear import of FGF 1. We also found that an nuclear localization sequence (NLS) in FGF 1, Ran GTPase , karyopherin‐α1 ( Kpn α1), and Kpn β1 were required for nuclear import of FGF 1. Nuclear import of exogenous FGF 2, which depends on CEP 57/ Translokin , was independent of LRRC 59, but was dependent on Kpn α1 and Kpn β1, while the nuclear import of FGF 1 was independent of CEP 57. LRRC 59 is a membrane‐anchored protein that localizes to the endoplasmic reticulum ( ER ) and the nuclear envelope ( NE ). We found that LRRC 59 possesses NLS ‐like sequences in its cytosolic part that can mediate nuclear import of soluble LRRC 59 variants, and that the localization of LRRC 59 to the NE depends on Kpn β1. We propose that LRRC 59 facilitates transport of cytosolic FGF 1 through nuclear pores by interaction with Kpns and movement of LRRC 59 along the ER and NE membranes.