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Nuclear Transport of Kir/Gem Requires Specific Signals and Importin α5 and Is Regulated by Calmodulin and Predicted Serine Phosphorylations
Author(s) -
Mahalakshmi Ramasubbu N.,
Nagashima Kazuaki,
Ng Mei Yong,
Inagaki Nobuya,
Hunziker Walter,
Béguin Pascal
Publication year - 2007
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.1600-0854.2007.00598.x
Subject(s) - importin , biology , calmodulin , nuclear transport , serine , microbiology and biotechnology , phosphorylation , cell nucleus , biochemistry , nucleus , enzyme
Kir/Gem, together with Rad, Rem and Rem2, is a member of the RGK small GTP‐binding protein family. These multifunctional proteins regulate voltage‐gated calcium channel (VGCC) activity and cell‐shape remodeling. Calmodulin and 14‐3‐3 binding modulate the functions of RGK proteins. Intriguingly, abolishing the binding of calmodulin or calmodulin and 14‐3‐3 results in nuclear accumulation of RGK proteins. Under certain conditions, the Ca v β3‐subunit of VGCCs can be translocated into the nucleus along with the RGK proteins, resulting in channel inactivation. The mechanism by which nuclear localization of RGK proteins is accomplished and regulated, however, is unknown. Here, we identify specific nuclear localization signals (NLS) in Kir/Gem that are both required and sufficient for nuclear transport. Importin α5 binds to Kir/Gem, and its depletion using RNA interference impairs nuclear translocation of this RGK protein. Calmodulin and predicted phosphorylations on serine residues within or in the vicinity of a C‐terminal bipartite NLS regulate nuclear translocation by interfering with the association between importin α 5 and Kir/Gem. These predicted phosphorylations, however, do not affect Kir/Gem‐mediated calcium channel downregulation but rather, as shown in the accompanying paper (Mahalakshmi RN, Ng MY, Guo K, Qi Z, Hunziker W, Béguin P. Nuclear localization of endogenous RGK proteins and modulation of cell shape remodeling by regulated nuclear transport. Traffic 2007; doi:10.1111/j.1600‐0854.2007.00599.x), interfere with cell‐shape remodeling.