Claus Munck Petersen

σ1B adaptin regulates adipogenesis by mediating the sorting of sortilin in adipose tissue

Research output: Contribution to journal/Conference contribution in journal/Contribution to newspaperJournal articleResearchpeer-review

  • Jennifer Baltes, Georg-August University Göttingen, Department for Cellular Biochemistry, Humboldtallee 23, D-37073 Göttingen, Germany., Unknown
  • Jakob Vejby Larsen, Denmark
  • Karthikeyan Radhakrishnan, Georg-August University Göttingen, Department for Cellular Biochemistry, Humboldtallee 23, D-37073 Göttingen, Germany., Unknown
  • Constanze Geumann, Georg-August University Göttingen, Department for Cellular Biochemistry, Humboldtallee 23, D-37073 Göttingen, Germany., Unknown
  • Manuel Kratzke, Georg-August University Göttingen, Department for Cellular Biochemistry, Humboldtallee 23, D-37073 Göttingen, Germany., Unknown
  • Claus Munck Petersen
  • Peter Schu, Georg-August University Göttingen, Department for Cellular Biochemistry, Humboldtallee 23, D-37073 Göttingen, Germany pschu@gwdg.de.

Here, we describe altered sorting of sortilin in adipocytes deficient for the σ1B-containing AP-1 complex, leading to the inhibition of adipogenesis. The AP-1 complex mediates protein sorting between the trans-Golgi network and endosomes. Vertebrates express three AP1 σ1 subunit isoforms - σ1A, σ1B and σ1C (also known as AP1S1, AP1S2 and AP1S3, respectively). σ1B-deficient mice display impaired recycling of synaptic vesicles and lipodystrophy. Here, we show that sortilin is overexpressed in adipose tissue from σ1B(-/-) mice, and that its overexpression in wild-type cells is sufficient to suppress adipogenesis. σ1B-specific binding of sortilin requires the sortilin DxxD-x12-DSxxxL motif. σ1B deficiency does not lead to a block of sortilin transport out of a specific organelle, but the fraction that reaches lysosomes is reduced. Sortilin binds to the receptor DLK1, an inhibitor of adipocyte differentiation, and the overexpression of sortilin prevents DLK1 downregulation, leading to enhanced inhibition of adipogenesis. DLK1 and sortilin expression are not increased in the brain tissue of σ1B(-/-) mice, although this is the tissue with the highest expression of σ1B and sortilin. Thus, adipose-tissue-specific and σ1B-dependent routes for the transport of sortilin exist and are involved in the regulation of adipogenesis and adipose-tissue mass.

Original languageEnglish
JournalJournal of Cell Science
Volume127
IssuePt 16
Pages (from-to)3477-87
Number of pages11
ISSN0021-9533
DOIs
Publication statusPublished - 15 Aug 2014

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