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Rab6‐Mediated Retrograde Transport Regulates Inner Nuclear Membrane Targeting of Caveolin‐2 in Response to Insulin
Author(s) -
Jeong Kyuho,
Kwon Hayeong,
Lee Jaewoong,
Jang Donghwan,
Hwang Eun Mi,
Park JaeYong,
Pak Yunbae
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.1600-0854.2012.01378.x
Subject(s) - microbiology and biotechnology , biology , golgi apparatus , endoplasmic reticulum , inner membrane , nuclear transport , nocodazole , cell nucleus , nucleus , biochemistry , mitochondrion , cell , cytoskeleton
Here, we have identified a retrograde transport pathway of caveolin‐2 (cav‐2) for its regulatory function in the nucleus. Confocal microscopy analysis, photoactivation experiments and subcellular fractionation revealed that cav‐2 localized in the Golgi was transported to the inner nuclear membrane ( INM ) in response to insulin. Exogenous caveolin‐1 (cav‐1) and P132L ‐cav‐1 expression did not affect the Golgi localization and insulin‐induced INM targeting of cav‐2. Cav‐ 2 DKV mutant in the endoplasmic reticulum ( ER ) was unable to translocate to the INM in response to insulin. The GTP ‐bound form of Rab6 promoted, but Rab6 siRNA and the GDP ‐bound form of Rab6 abrogated, retrograde trafficking of cav‐2 from the Golgi to ER . Colchicine or nocodazole treatment abolished insulin‐induced INM targeting of cav‐2. Knock down of gp210 inhibited insulin‐induced import of cav‐2 from ER /outer nuclear membrane ( ONM ) to the INM . The INM ‐targeted cav‐2 prevented heterochromatinization and promoted transcriptional activation of Elk‐1 and signal transducer and activator of transcription 3 ( STAT3 ). The results provide molecular mechanisms for insulin‐induced INM translocation of cav‐2 initiated (i) by Golgi‐to‐ ER retrograde trafficking of cav‐2 via microtubule‐based Rab6‐ GTP ‐dependent transport and subsequently processed (ii) by gp210‐mediated import of cav‐2 from ER / ONM to INM .