Genetic diversity of CHC22 clathrin impacts its function in glucose metabolism
2019
CHC22
clathrinplays a key role in intracellular membrane traffic of the insulin-responsive
glucose transporter
GLUT4in humans. We performed population genetic and phylogenetic analyses of the CHC22-encoding CLTCL1 gene, revealing independent gene loss in at least two vertebrate lineages, after arising from
gene duplication. All vertebrates retained the paralogous
CLTCgene encoding CHC17
clathrin, which mediates endocytosis. For vertebrates retaining CLTCL1, strong evidence for purifying selection supports CHC22 functionality. All human populations maintained two high frequency CLTCL1 allelic variants, encoding either methionine or valine at position 1316. Functional studies indicated that CHC22-V1316, which is more frequent in farming populations than in
hunter-gatherers, has different cellular dynamics than M1316-CHC22 and is less effective at controlling
GLUT4membrane traffic, attenuating its insulin-regulated response. These analyses suggest that ancestral human dietary change influenced selection of
allotypesthat affect CHC229s role in metabolism and have potential to differentially influence the human insulin response.
Keywords:
-
Correction
-
Source
-
Cite
-
Save
1
References
0
Citations
NaN
KQI