The clathrin heavy chain isoform CHC22 functions in a novel endosomal sorting step
570
0303 health sciences
Glucose Transporter Type 4
1.1 Normal biological development and functioning
610
Biological Transport
Endosomes
Biological Sciences
Medical and Health Sciences
Cell Line
Myoblasts
Mice
03 medical and health sciences
Underpinning research
Clathrin Heavy Chains
Animals
Humans
Research Articles
Developmental Biology
trans-Golgi Network
DOI:
10.1083/jcb.200908057
Publication Date:
2010-01-11T19:05:44Z
AUTHORS (4)
ABSTRACT
Clathrin heavy chain 22 (CHC22) is an isoform of the well-characterized CHC17 clathrin heavy chain, a coat component of vesicles that mediate endocytosis and organelle biogenesis. CHC22 has a distinct role from CHC17 in trafficking glucose transporter 4 (GLUT4) in skeletal muscle and fat, though its transfection into HEK293 cells suggests functional redundancy. Here, we show that CHC22 is eightfold less abundant than CHC17 in muscle, other cell types have variably lower amounts of CHC22, and endogenous CHC22 and CHC17 function independently in nonmuscle and muscle cells. CHC22 was required for retrograde trafficking of certain cargo molecules from endosomes to the trans-Golgi network (TGN), defining a novel endosomal-sorting step distinguishable from that mediated by CHC17 and retromer. In muscle cells, depletion of syntaxin 10 as well as CHC22 affected GLUT4 targeting, establishing retrograde endosome–TGN transport as critical for GLUT4 trafficking. Like CHC22, syntaxin 10 is not expressed in mice but is present in humans and other vertebrates, implicating two species-restricted endosomal traffic proteins in GLUT4 transport.
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