Identification of VPS13C as a Galectin-12-Binding Protein That Regulates Galectin-12 Protein Stability and Adipogenesis |
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| Authors: | Ri-Yao Yang Huiting Xue Lan Yu Antonio Velayos-Baeza Anthony P Monaco Fu-Tong Liu |
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| Institution: | 1Department of Dermatology, School of Medicine, University of California-Davis, Sacramento, California, 95817, United States of America;2School of Life Sciences, Northeast Normal University, Changchun, 130024, People’s Republic of China;3Wellcome Trust Centre for Human Genetics, OX3 7BN, Oxford, United Kingdom;4Institute of Biomedical Sciences, Academia Sinica, Nankang, Taipei, 115, Taiwan;University of Liverpool, UNITED KINGDOM |
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| 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. |
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