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

Stéphane M Camus (1, 2) , Marine Camus (1, 2) , Carmen Figueras-Novoa (2) , Gaelle Boncompain (3) , L. Amanda Sadacca (2) , Christopher Esk (4) , Anne Bigot (5) , Gwyn W Gould (6, 7) , Dimitrios Kioumourtzoglou (6, 7, 8) , Franck Perez (3) , Nia J Bryant (8) , Shaeri Mukherjee (1) , Frances M Brodsky (1, 2)

1 UC San Francisco - University of California [San Francisco]
2 UCL - University College of London [London]
3 Institut Curie [Paris]
4 OeAW - Austrian Academy of Sciences
5 Centre de recherche en Myologie – U974 SU-INSERM
6 College of Medical, Veterinary and Life Sciences [Glasgow]
7 University of Glasgow
8 University of York [York, UK]

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.

Domaines: Sciences du Vivant [q-bio]; Médecine humaine et pathologie

Stéphane M Camus, Marine Camus, Carmen Figueras-Novoa, Gaelle Boncompain, L. Amanda Sadacca, et al.. CHC22 clathrin mediates traffic from early secretory compartments for human GLUT4 pathway biogenesis. Journal of Cell Biology, 2020, 219 (1), ⟨10.1083/jcb.201812135⟩. ⟨hal-02555498⟩