Open AccessIdentification of VPS13C as a Galectin-12-Binding Protein That Regulates Galectin-12 Protein Stability and Adipogenesis
Author(s) -
Ri Yao Yang,
Huiting Xue,
Liang Yu,
Antonio VelayosBaeza,
Anthony P. Monaco,
Fu Tong Liu
Publication year - 2016
Publication title -
plos one
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.99
H-Index - 332
ISSN - 1932-6203
DOI - 10.1371/journal.pone.0153534
Subject(s) - adipogenesis , adipocyte , downregulation and upregulation , microbiology and biotechnology , gene knockdown , galectin , biology , binding protein , protein family , glucose homeostasis , biochemistry , adipose tissue , insulin , endocrinology , insulin resistance , apoptosis , mesenchymal stem cell , gene
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.