ArticleTraffic (Copenhagen, Denmark)2020
Genetic evidence for an inhibitory role of tomosyn in insulin-stimulated GLUT4 exocytosis.
Article in Traffic (Copenhagen, Denmark), 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.
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Who cites it
8 citing papers in PubMed, 14 citations in OpenAlex.
- Photosensitive Nanoprobes for Rapid Isolation and Size-Specific Enrichment of Synthetic and Extracellular Vesicle Subpopulations.Advanced functional materials · 2024Article
- Tomosyns attenuate SNARE assembly and synaptic depression by binding to VAMP2-containing template complexes.Nature communications · 2024Article
- The Role of Tomosyn in the Regulation of Neurotransmitter Release.Advances in neurobiology · 2023Article
- Epigallocatechin gallate inhibits SNARE-dependent membrane fusion by blocking trans-SNARE assembly.FEBS open bio · 2022Article
- The evolving view of thermogenic fat and its implications in cancer and metabolic diseases.Signal transduction and targeted therapy · 2022Review
- Cryo-EM structure of human glucose transporter GLUT4.Nature communications · 2022Article
- GLUT4 On the move.The Biochemical journal · 2022Article
- Exocytosis Proteins: Typical and Atypical Mechanisms of Action in Skeletal Muscle.Frontiers in endocrinology · 2022Review
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Authors and funding
7 authors at 2 institutions in 2 countries.
Funding
Abstract
Exocytosis is a vesicle fusion process driven by soluble N-ethylmaleimide-sensitive factor attachment protein receptors (SNAREs). A classic exocytic pathway is insulin-stimulated translocation of the glucose transporter type 4 (GLUT4) from intracellular vesicles to the plasma membrane in adipocytes and skeletal muscles. The GLUT4 exocytic pathway plays a central role in maintaining blood glucose homeostasis and is compromised in insulin resistance and type 2 diabetes. A candidate regulator of GLUT4 exocytosis is tomosyn, a soluble protein expressed in adipocytes. Tomosyn directly binds to GLUT4 exocytic SNAREs in vitro but its role in GLUT4 exocytosis was unknown. In this work, we used CRISPR-Cas9 genome editing to delete the two tomosyn-encoding genes in adipocytes. We observed that both basal and insulin-stimulated GLUT4 exocytosis was markedly elevated in the double knockout (DKO) cells. By contrast, adipocyte differentiation and insulin signaling remained intact in the DKO adipocytes. In a reconstituted liposome fusion assay, tomosyn inhibited all the SNARE complexes underlying GLUT4 exocytosis. The inhibitory activity of tomosyn was relieved by NSF and α-SNAP, which act in concert to remove tomosyn from GLUT4 exocytic SNAREs. Together, these studies revealed an inhibitory role for tomosyn in insulin-stimulated GLUT4 exocytosis in adipocytes. We suggest that tomosyn-arrested SNAREs represent a reservoir of fusion capacity that could be harnessed to treat patients with insulin resistance and type 2 diabetes.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.