TY - JOUR
T1 - Identification of VPS13C as a galectin-12- binding protein that regulates galectin-12 protein stability and adipogenesis
AU - Yang, Ri Yao
AU - Xue, Huiting
AU - Yu, Lan
AU - Velayos-Baeza, Antonio
AU - Monaco, Anthony P.
AU - Liu, Fu Tong
N1 - Funding Information:
This research was supported by National Institutes of Health Grant R01 AI020958 and R01 AR56343 (to F.-T.L.), the Harrison Endowed Chair for Diabetes Research Award (to R.-Y.Y.), the Wellcome Trust core grant 075491/Z/04 and the Advocacy for Neuroacanthocytosis Patients (to A.P.M. and A.V.-B.). We thank Dr. Louise Bird and the Oxford Protein Production Facility staff for their technical support.
Publisher Copyright:
© 2016 Yang et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
PY - 2016/4
Y1 - 2016/4
N2 - Galectin-12, a member of the galectin family of β-galactoside-binding animal lectins, is preferentially expressed in adipocytes and required for adipocyte differentiation in vitro. This protein was recently found to regulate lipolysis, whole body adiposity, and glucose homeostasis in vivo. Here we identify VPS13C, a member of the VPS13 family of vacuolar protein sorting-associated proteins highly conserved throughout eukaryotic evolution, as a major galectin-12-binding protein. VPS13C is upregulated during adipocyte differentiation, and is required for galectin-12 protein stability. Knockdown of Vps13c markedly reduces the steady-state levels of galectin-12 by promoting its degradation through primarily the lysosomal pathway, and impairs adipocyte differentiation. Our studies also suggest that VPS13C may have a broader role in protein quality control. The regulation of galectin-12 stability by VPS13C could potentially be exploited for therapeutic intervention of obesity and related metabolic diseases.
AB - Galectin-12, a member of the galectin family of β-galactoside-binding animal lectins, is preferentially expressed in adipocytes and required for adipocyte differentiation in vitro. This protein was recently found to regulate lipolysis, whole body adiposity, and glucose homeostasis in vivo. Here we identify VPS13C, a member of the VPS13 family of vacuolar protein sorting-associated proteins highly conserved throughout eukaryotic evolution, as a major galectin-12-binding protein. VPS13C is upregulated during adipocyte differentiation, and is required for galectin-12 protein stability. Knockdown of Vps13c markedly reduces the steady-state levels of galectin-12 by promoting its degradation through primarily the lysosomal pathway, and impairs adipocyte differentiation. Our studies also suggest that VPS13C may have a broader role in protein quality control. The regulation of galectin-12 stability by VPS13C could potentially be exploited for therapeutic intervention of obesity and related metabolic diseases.
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U2 - 10.1371/journal.pone.0153534
DO - 10.1371/journal.pone.0153534
M3 - Article
C2 - 27073999
AN - SCOPUS:84963620416
SN - 1932-6203
VL - 11
JO - PloS one
JF - PloS one
IS - 4
M1 - e0153534
ER -