Sorting of GLUT4 into its insulin-sensitive store requires the Sec1/Munc18 protein mVps45

Jennifer Roccisana, Jessica B. A. Sadler, Nia J. Bryant, Gwyn W. Gould

Research output: Contribution to journalArticle

10 Citations (Scopus)

Abstract

Insulin stimulates glucose transport in fat and muscle cells by regulating delivery of the facilitative glucose transporter, glucose transporter isoform 4 (GLUT4), to the plasma membrane. In the absence of insulin, GLUT4 is sequestered away from the general recycling endosomal pathway into specialized vesicles, referred to as GLUT4-storage vesicles. Understanding the sorting of GLUT4 into this store is a major challenge. Here we examine the role of the Sec1/Munc18 protein mVps45 in GLUT4 trafficking. We show that mVps45 is up-regulated upon differentiation of 3T3-L1 fibroblasts into adipocytes and is expressed at stoichiometric levels with its cognate target-soluble N-ethylmaleimide-sensitive factor attachment protein receptor, syntaxin 16. Depletion of mVps45 in 3T3-L1 adipocytes results in decreased GLUT4 levels and impaired insulin-stimulated glucose transport. Using subcellular fractionation and an in vitro assay for GLUT4-storage vesicle formation, we show that mVps45 is required to correctly traffic GLUT4 into this compartment. Collectively our data reveal a crucial role for mVps45 in the delivery of GLUT4 into its specialized, insulin-regulated compartment.

Original languageEnglish
Pages (from-to)2389-2397
Number of pages9
JournalMolecular Biology of the Cell
Volume24
Issue number15
DOIs
Publication statusPublished - 1 Aug 2013

Fingerprint

Munc18 Proteins
Facilitative Glucose Transport Proteins
Protein Isoforms
Insulin
Adipocytes
Syntaxin 16
SNARE Proteins
Glucose
Recycling
Muscle Cells

Keywords

  • GLUT4
  • insulin
  • glucose transport

Cite this

Roccisana, Jennifer ; Sadler, Jessica B. A. ; Bryant, Nia J. ; Gould, Gwyn W. / Sorting of GLUT4 into its insulin-sensitive store requires the Sec1/Munc18 protein mVps45. In: Molecular Biology of the Cell. 2013 ; Vol. 24, No. 15. pp. 2389-2397.
@article{9d45bee4d8d54755882a0096b8c233ee,
title = "Sorting of GLUT4 into its insulin-sensitive store requires the Sec1/Munc18 protein mVps45",
abstract = "Insulin stimulates glucose transport in fat and muscle cells by regulating delivery of the facilitative glucose transporter, glucose transporter isoform 4 (GLUT4), to the plasma membrane. In the absence of insulin, GLUT4 is sequestered away from the general recycling endosomal pathway into specialized vesicles, referred to as GLUT4-storage vesicles. Understanding the sorting of GLUT4 into this store is a major challenge. Here we examine the role of the Sec1/Munc18 protein mVps45 in GLUT4 trafficking. We show that mVps45 is up-regulated upon differentiation of 3T3-L1 fibroblasts into adipocytes and is expressed at stoichiometric levels with its cognate target-soluble N-ethylmaleimide-sensitive factor attachment protein receptor, syntaxin 16. Depletion of mVps45 in 3T3-L1 adipocytes results in decreased GLUT4 levels and impaired insulin-stimulated glucose transport. Using subcellular fractionation and an in vitro assay for GLUT4-storage vesicle formation, we show that mVps45 is required to correctly traffic GLUT4 into this compartment. Collectively our data reveal a crucial role for mVps45 in the delivery of GLUT4 into its specialized, insulin-regulated compartment.",
keywords = "GLUT4, insulin, glucose transport",
author = "Jennifer Roccisana and Sadler, {Jessica B. A.} and Bryant, {Nia J.} and Gould, {Gwyn W.}",
year = "2013",
month = "8",
day = "1",
doi = "10.1091/mbc.E13-01-0011",
language = "English",
volume = "24",
pages = "2389--2397",
journal = "Molecular Biology of the Cell",
issn = "1059-1524",
publisher = "American Society for Cell Biology",
number = "15",

}

Sorting of GLUT4 into its insulin-sensitive store requires the Sec1/Munc18 protein mVps45. / Roccisana, Jennifer; Sadler, Jessica B. A.; Bryant, Nia J.; Gould, Gwyn W.

In: Molecular Biology of the Cell, Vol. 24, No. 15, 01.08.2013, p. 2389-2397.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Sorting of GLUT4 into its insulin-sensitive store requires the Sec1/Munc18 protein mVps45

AU - Roccisana, Jennifer

AU - Sadler, Jessica B. A.

AU - Bryant, Nia J.

AU - Gould, Gwyn W.

PY - 2013/8/1

Y1 - 2013/8/1

N2 - Insulin stimulates glucose transport in fat and muscle cells by regulating delivery of the facilitative glucose transporter, glucose transporter isoform 4 (GLUT4), to the plasma membrane. In the absence of insulin, GLUT4 is sequestered away from the general recycling endosomal pathway into specialized vesicles, referred to as GLUT4-storage vesicles. Understanding the sorting of GLUT4 into this store is a major challenge. Here we examine the role of the Sec1/Munc18 protein mVps45 in GLUT4 trafficking. We show that mVps45 is up-regulated upon differentiation of 3T3-L1 fibroblasts into adipocytes and is expressed at stoichiometric levels with its cognate target-soluble N-ethylmaleimide-sensitive factor attachment protein receptor, syntaxin 16. Depletion of mVps45 in 3T3-L1 adipocytes results in decreased GLUT4 levels and impaired insulin-stimulated glucose transport. Using subcellular fractionation and an in vitro assay for GLUT4-storage vesicle formation, we show that mVps45 is required to correctly traffic GLUT4 into this compartment. Collectively our data reveal a crucial role for mVps45 in the delivery of GLUT4 into its specialized, insulin-regulated compartment.

AB - Insulin stimulates glucose transport in fat and muscle cells by regulating delivery of the facilitative glucose transporter, glucose transporter isoform 4 (GLUT4), to the plasma membrane. In the absence of insulin, GLUT4 is sequestered away from the general recycling endosomal pathway into specialized vesicles, referred to as GLUT4-storage vesicles. Understanding the sorting of GLUT4 into this store is a major challenge. Here we examine the role of the Sec1/Munc18 protein mVps45 in GLUT4 trafficking. We show that mVps45 is up-regulated upon differentiation of 3T3-L1 fibroblasts into adipocytes and is expressed at stoichiometric levels with its cognate target-soluble N-ethylmaleimide-sensitive factor attachment protein receptor, syntaxin 16. Depletion of mVps45 in 3T3-L1 adipocytes results in decreased GLUT4 levels and impaired insulin-stimulated glucose transport. Using subcellular fractionation and an in vitro assay for GLUT4-storage vesicle formation, we show that mVps45 is required to correctly traffic GLUT4 into this compartment. Collectively our data reveal a crucial role for mVps45 in the delivery of GLUT4 into its specialized, insulin-regulated compartment.

KW - GLUT4

KW - insulin

KW - glucose transport

UR - http://www.scopus.com/inward/record.url?scp=84881061444&partnerID=8YFLogxK

U2 - 10.1091/mbc.E13-01-0011

DO - 10.1091/mbc.E13-01-0011

M3 - Article

VL - 24

SP - 2389

EP - 2397

JO - Molecular Biology of the Cell

JF - Molecular Biology of the Cell

SN - 1059-1524

IS - 15

ER -