Identification of VPS13C as a Galectin-12-Binding Protein That Regulates Galectin-12 Protein Stability and Adipogenesis

• Published in: PloS one Vol. 11; no. 4; p. e0153534
• Main Authors: Yang, Ri-Yao, Xue, Huiting, Yu, Lan, Velayos-Baeza, Antonio, Monaco, Anthony P, Liu, Fu-Tong
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 13-04-2016; Public Library of Science (PLoS)
• Subjects: 3T3-L1 Cells; Adipocytes; Adipogenesis; Adipogenesis - genetics; Adipose tissue; Alzheimer's disease; Animals; Apoptosis; Binding; Binding proteins; Biology and Life Sciences; Cell death; Chemical properties; Cloning; Control stability; Deoxyribonucleic acid; Dermatology; Diabetes; Differentiation; DNA; DNA polymerase; Galectins - genetics; Galectins - metabolism; Genetic aspects; Genomes; Homeostasis; Immunoglobulins; Insulin resistance; Lectins; Lipolysis; Medicine; Medicine and Health Sciences; Metabolic disorders; Metabolism; Mice; Mutation; Nerve Tissue Proteins - genetics; Nerve Tissue Proteins - metabolism; Physiological aspects; Protein Stability; Protein transport; Proteins; Proteins - genetics; Proteins - metabolism; Quality control; Research and Analysis Methods; Vesicular Transport Proteins; United States; Taiwan; Sacramento California; California; United Kingdom > UK; United States > US
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0153534

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.