title: Identification of VPS13C as a Galectin-12-Binding Protein That Regulates Galectin-12 Protein Stability and Adipogenesis.
abstract: 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.
authors.affiliation: Department of Dermatology, School of Medicine, University of California-Davis, Sacramento, California, 95817, United States of America.
authors.forename: Ri-Yao
authors.initials: RY
authors.lastname: Yang
authors.affiliation: Department of Dermatology, School of Medicine, University of California-Davis, Sacramento, California, 95817, United States of America.|School of Life Sciences, Northeast Normal University, Changchun, 130024, People's Republic of China.
authors.forename: Huiting
authors.initials: H
authors.lastname: Xue
authors.affiliation: Department of Dermatology, School of Medicine, University of California-Davis, Sacramento, California, 95817, United States of America.
authors.forename: Lan
authors.initials: L
authors.lastname: Yu
authors.affiliation: Wellcome Trust Centre for Human Genetics, OX3 7BN, Oxford, United Kingdom.
authors.forename: Antonio
authors.initials: A
authors.lastname: Velayos-Baeza
authors.affiliation: Wellcome Trust Centre for Human Genetics, OX3 7BN, Oxford, United Kingdom.
authors.forename: Anthony P
authors.initials: AP
authors.lastname: Monaco
authors.affiliation: Department of Dermatology, School of Medicine, University of California-Davis, Sacramento, California, 95817, United States of America.|Institute of Biomedical Sciences, Academia Sinica, Nankang, Taipei, 115, Taiwan.
authors.forename: Fu-Tong
authors.initials: FT
authors.lastname: Liu
mesh_terms: D041721:3T3-L1 Cells; D050156:Adipogenesis / Q000235:genetics*; D000818:Animals; D037161:Galectins / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D055550:Protein Stability; D011506:Proteins / Q000235:genetics / Q000378:metabolism*; D033921:Vesicular Transport Proteins
chemical_list: D037161:Galectins; D009419:Nerve Tissue Proteins; D011506:Proteins; D033921:Vesicular Transport Proteins; C497828:Vps13a protein, mouse