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Biochemical and Biophysical Research Communications
Volume 405, Issue 1, 4 February 2011, Pages 96–101
Vimentin binds IRAP and is involved in GLUT4 vesicle trafficking
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Yohko Hirata
Toshio Hosaka
Takeo Iwatac
Chung T.K. Le
Bayasgalan Jambaldorj
Kiyoshi Teshigawara,
Nagakatsu Harada
Hiroshi Sakaue
Tohru Sakai,
Katsuhiko Yoshimoto
Yutaka Nakaya
ABSTRACT
Insulin-responsive aminopeptidase (IRAP) and GLUT4 are two major cargo proteins of GLUT4
storage vesicles (GSVs) that are translocated from a postendosomal storage compartment to the
plasma membrane (PM) in response to insulin. The cytoplasmic region of IRAP is reportedly
involved in retention of GSVs. In this study, vimentin was identified using the cytoplasmic
domain of IRAP as bait. The validity of this interaction was confirmed by pull-down assays and
immunoprecipitation in 3T3-L1 adipocytes. In addition, it was shown that GLUT4 translocation
to the PM by insulin was decreased in vimentin-depleted adipocytes, presumably due to
dispersing GSVs away from the cytoskeleton. These findings suggest that the IRAP binding
protein, vimentin, plays an important role in retention of GSVs.
The Journal of Medical Investigation
Vol. 60 (2013) No. 3.4 p. 197-204
Cysteine string protein 1 (CSP1) modulates insulin sensitivity by attenuating
glucose transporter 4 (GLUT4) vesicle docking with the plasma membrane
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Bayasgalan Jambaldorj
Eri Terada
Toshio Hosaka
Yuka Kishuku
Yukiko Tomioka
Kaori Iwashima
Yohko Hirata
Kiyoshi Teshigawara
Chung Thi Kim Le
Tadahiko Nakagawa
Nagakatsu Harada
Tohru Sakai
Hiroshi Sakaue
Toshio Matsumoto
Makoto Funaki
Akira Takahashi
Yutaka Nakaya
ABSTRACT
Insulin stimulates glucose transporter 4 (GLUT4) vesicle recruitment from its intracellular
storage site to the plasma membrane. Cysteine string protein 1 (CSP1) is a SNARE-binding
protein involved in the vesicular trafficking of neurotransmitters and other exocytic processes. In
this study, we investigated the involvement of CSP1 in insulin-dependent GLUT4 recruitment in
3T3-L1 adipocytes. Over-expression of wild-type CSP1 led to attenuated insulin-stimulated
glucose uptake without any change in GLUT4 content in the plasma membrane, rather it inhibits
docking by blocking the association of VAMP2 with syntaxin 4. In contrast, knockdown of
CSP1 enhanced insulin-stimulated glucose uptake. The mRNA and protein expression of CSP1
was elevated in 3T3-L1 adipocytes in insulin resistant states caused by high levels of palmitate
and chronic insulin exposure. Taken together, the results of this study suggest that CSP1 is
involved in insulin resistance by interrupting GLUT4 vesicle docking with the plasma
membrane. J. Med. Invest. 60: 197-204, August, 2013