CHC22 clathrin mediates traffic from early secretory compartments for human GLUT4 pathway biogenesis

TY - JOUR

T1 - CHC22 clathrin mediates traffic from early secretory compartments for human GLUT4 pathway biogenesis

AU - Camus, Stéphane M

AU - Camus, Marine D

AU - Figueras-Novoa, Carmen

AU - Boncompain, Gaelle

AU - Sadacca, L Amanda

AU - Esk, Christopher

AU - Bigot, Anne

AU - Gould, Gwyn W

AU - Kioumourtzoglou, Dimitrios

AU - Perez, Franck

AU - Bryant, Nia J

AU - Mukherjee, Shaeri

AU - Brodsky, Frances M

N1 - This is an author-produced version of the published paper. Uploaded in accordance with the publisher’s self-archiving policy. Further copying may not be permitted; contact the publisher for details.

PY - 2020/1/6

Y1 - 2020/1/6

N2 - Glucose transporter 4 (GLUT4) is sequestered inside muscle and fat and then released by vesicle traffic to the cell surface in response to postprandial insulin for blood glucose clearance. Here, we map the biogenesis of this GLUT4 traffic pathway in humans, which involves clathrin isoform CHC22. We observe that GLUT4 transits through the early secretory pathway more slowly than the constitutively secreted GLUT1 transporter and localize CHC22 to the ER-to-Golgi intermediate compartment (ERGIC). CHC22 functions in transport from the ERGIC, as demonstrated by an essential role in forming the replication vacuole of Legionella pneumophila bacteria, which requires ERGIC-derived membrane. CHC22 complexes with ERGIC tether p115, GLUT4, and sortilin, and downregulation of either p115 or CHC22, but not GM130 or sortilin, abrogates insulin-responsive GLUT4 release. This indicates that CHC22 traffic initiates human GLUT4 sequestration from the ERGIC and defines a role for CHC22 in addition to retrograde sorting of GLUT4 after endocytic recapture, enhancing pathways for GLUT4 sequestration in humans relative to mice, which lack CHC22.

AB - Glucose transporter 4 (GLUT4) is sequestered inside muscle and fat and then released by vesicle traffic to the cell surface in response to postprandial insulin for blood glucose clearance. Here, we map the biogenesis of this GLUT4 traffic pathway in humans, which involves clathrin isoform CHC22. We observe that GLUT4 transits through the early secretory pathway more slowly than the constitutively secreted GLUT1 transporter and localize CHC22 to the ER-to-Golgi intermediate compartment (ERGIC). CHC22 functions in transport from the ERGIC, as demonstrated by an essential role in forming the replication vacuole of Legionella pneumophila bacteria, which requires ERGIC-derived membrane. CHC22 complexes with ERGIC tether p115, GLUT4, and sortilin, and downregulation of either p115 or CHC22, but not GM130 or sortilin, abrogates insulin-responsive GLUT4 release. This indicates that CHC22 traffic initiates human GLUT4 sequestration from the ERGIC and defines a role for CHC22 in addition to retrograde sorting of GLUT4 after endocytic recapture, enhancing pathways for GLUT4 sequestration in humans relative to mice, which lack CHC22.

KW - Adaptor Proteins, Vesicular Transport/metabolism

KW - Biosynthetic Pathways

KW - Cell Membrane/metabolism

KW - Clathrin/metabolism

KW - Clathrin Heavy Chains/metabolism

KW - Endoplasmic Reticulum/metabolism

KW - Glucose Transporter Type 4/metabolism

KW - Golgi Apparatus/metabolism

KW - HeLa Cells

KW - Humans

KW - Protein Transport

KW - Rho Guanine Nucleotide Exchange Factors/metabolism

KW - Vesicular Transport Proteins/metabolism

U2 - 10.1083/jcb.201812135

DO - 10.1083/jcb.201812135

M3 - Article

C2 - 31863584

SN - 0021-9525

VL - 219

JO - Journal of Cell Biology

JF - Journal of Cell Biology

IS - 1

M1 - e201812135

ER -