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

Stéphane M. Camus, Marine D. Camus, Carmen Figueras-Novoa, Gaelle Boncompain, L. Amanda Sadacca, Christopher Esk, Anne Bigot, Gwyn W. Gould, Dimitrios Kioumourtzoglou, Franck Perez, Nia J. Bryant, Shaeri Mukherjee, Frances M. Brodsky

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Abstract

Post-prandial blood glucose is cleared by Glucose Transporter 4 (GLUT4) released from an intracellular GLUT4 storage compartment (GSC) to the surface of muscle and adipose tissue in response to insulin. Here we map the biosynthetic pathway for human GSC formation, which involves the clathrin isoform CHC22. We observe that GLUT4 transits more slowly through the early secretory pathway than the constitutively-secreted GLUT1 transporter, and show CHC22 colocalizes with p115 in the endoplasmic-reticulum-to-Golgi-intermediate compartment (ERGIC). We find CHC22 functions in membrane traffic from the early secretory pathway during formation of the replication vacuole of Legionella pneumophila, which also acquires components of the GLUT4 pathway. We show that p115 but not GM130 is required for GSC formation, indicating GSC biogenesis from the ERGIC bypasses the Golgi. This GSC biogenesis pathway is attenuated in mice, which lack CHC22, and rely mainly on recapture of surface GLUT4 to populate their GSC. GLUT4 traffic to the GSC is enhanced by CHC22 function at the human ERGIC, which has implications for pathways to insulin resistance.
Original languageEnglish
Article numbere201812135
Number of pages21
JournalJournal of Cell Biology
Volume219
Issue number1
DOIs
Publication statusPublished - 19 Dec 2019

Keywords

  • glucose transporter 4
  • insulin
  • diabetes
  • membrane trafficking

Cite this

Camus, S. M., Camus, M. D., Figueras-Novoa, C., Boncompain, G., Sadacca, L. A., Esk, C., Bigot, A., Gould, G. W., Kioumourtzoglou, D., Perez, F., Bryant, N. J., Mukherjee, S., & Brodsky, F. M. (2019). CHC22 clathrin mediates traffic from early secretory compartments for human GLUT4 pathway biogenesis. Journal of Cell Biology, 219(1), [e201812135]. https://doi.org/10.1083/jcb.201812135