Phosphorylation of the N-terminus of Syntaxin-16 controls interaction with mVps45 and GLUT4 trafficking in adipocytes.

Autor:	Bremner SK; SIPBS, University of Strathclyde, Glasgow, United Kingdom., Berends R; Institute of Molecular, Cell and Systems Biology, University of Glasgow, Glasgow, United Kingdom., Kaupisch A; Institute of Molecular, Cell and Systems Biology, University of Glasgow, Glasgow, United Kingdom., Roccisana J; Institute of Molecular, Cell and Systems Biology, University of Glasgow, Glasgow, United Kingdom., Sutherland C; Department of Cellular Medicine, University of Dundee, Dundee, United Kingdom., Bryant NJ; Department of Biology, University of York, York, United Kingdom., Gould GW; SIPBS, University of Strathclyde, Glasgow, United Kingdom.
Jazyk:	angličtina
Zdroj:	PeerJ [PeerJ] 2023 Jul 24; Vol. 11, pp. e15630. Date of Electronic Publication: 2023 Jul 24 (Print Publication: 2023).
DOI:	10.7717/peerj.15630
Abstrakt:	The ability of insulin to stimulate glucose transport in muscle and fat cells is mediated by the regulated delivery of intracellular vesicles containing glucose transporter-4 (GLUT4) to the plasma membrane, a process known to be defective in disease such as Type 2 diabetes. In the absence of insulin, GLUT4 is sequestered in tubules and vesicles within the cytosol, collectively known as the GLUT4 storage compartment. A subset of these vesicles, known as the 'insulin responsive vesicles' are selectively delivered to the cell surface in response to insulin. We have previously identified Syntaxin16 (Sx16) and its cognate Sec1/Munc18 protein family member mVps45 as key regulatory proteins involved in the delivery of GLUT4 into insulin responsive vesicles. Here we show that mutation of a key residue within the Sx16 N-terminus involved in mVps45 binding, and the mutation of the Sx16 binding site in mVps45 both perturb GLUT4 sorting, consistent with an important role of the interaction of these two proteins in GLUT4 trafficking. We identify Threonine-7 (T7) as a site of phosphorylation of Sx16 in vitro . Mutation of T7 to D impairs Sx16 binding to mVps45 in vitro and overexpression of T7D significantly impaired insulin-stimulated glucose transport in adipocytes. We show that both AMP-activated protein kinase (AMPK) and its relative SIK2 phosphorylate this site. Our data suggest that Sx16 T7 is a potentially important regulatory site for GLUT4 trafficking in adipocytes. Competing Interests: Gwyn W Gould is an Academic Editor for PeerJ. (©2023 Bremner et al.)
Databáze:	MEDLINE
Externí odkaz:	Zobrazit plný text záznamu