Septin 7 reduces nonmuscle myosin IIA activity in the SNAP23 complex and hinders GLUT4 storage vesicle docking and fusion

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Wasik , A , Dumont , V , Tienari , J-P , Nyman , T A , Fogarty , C , Forsblom , C , Lehto , M , Lehtonen , E , Groop , P-H & Lehtonen , S 2017 , ' Septin 7 reduces nonmuscle myosin IIA activity in the SNAP23 complex and hinders GLUT4 storage vesicle docking and fusion ' , Experimental Cell Research , vol. 350 , no. 2 , pp. 336-348 . https://doi.org/10.1016/j.yexcr.2016.12.010

Title: Septin 7 reduces nonmuscle myosin IIA activity in the SNAP23 complex and hinders GLUT4 storage vesicle docking and fusion
Author: Wasik, Anita; Dumont, Vincent; Tienari, Jukka-Pekka; Nyman, Tuula A.; Fogarty, Christopher; Forsblom, Carol; Lehto, Markku; Lehtonen, Eero; Groop, Per-Henrik; Lehtonen, Sanna
Contributor organization: Department of Pathology
Medicum
Sanna Lehtonen research group
Clinicum
Institute of Biotechnology
Diabetes and Obesity Research Program
Research Programs Unit
Nefrologian yksikkö
Department of Medicine
Per Henrik Groop / Principal Investigator
HUS Abdominal Center
HUS Internal Medicine and Rehabilitation
Date: 2017-01-15
Language: eng
Number of pages: 13
Belongs to series: Experimental Cell Research
ISSN: 0014-4827
DOI: https://doi.org/10.1016/j.yexcr.2016.12.010
URI: http://hdl.handle.net/10138/175468
Abstract: Glomerular epithelial cells, podocytes, are insulin responsive and can develop insulin resistance. Here, we demonstrate that the small GTPase septin 7 forms a complex with nonmuscle myosin heavy chain HA (NMHC-HA; encoded by MYH9), a component of the nonmuscle myosin HA (NM-IIA) hexameric complex. We observed that knockdown of NMHC-IIA decreases insulin-stimulated glucose uptake into podocytes. Both septin 7 and NM-IIA associate with SNAP23, a SNARE protein involved in GLUT4 storage vesicle (GSV) docking and fusion with the plasma membrane. We observed that insulin decreases the level of septin 7 and increases the activity of NM-IIA in the SNAP23 complex, as visualized by increased phosphorylation of myosin regulatory light chain. Also knockdown of septin 7 increases the activity of NM-IIA in the complex. The activity of NM-IIA is increased in diabetic rat glomeruli and cultured human podocytes exposed to macroalbuminuric sera from patients with type 1 diabetes. Collectively, the data suggest that the activity of NM-IIA in the SNAP23 complex plays a key role in insulin-stimulated glucose uptake into podocytes. Furthermore, we observed that septin 7 reduces the activity of NM-IIA in the SNAP23 complex and thereby hinders GSV docking and fusion with the plasma membrane.
Subject: Septin 7
Nonmuscle myosin IIA
GLUT4 storage vesicle
SNARE
Glucose uptake
Podocytes
PODOCYTE-SPECIFIC DELETION
STIMULATED GLUCOSE-UPTAKE
INSULIN-RESISTANCE
LEUKOCYTE INCLUSIONS
GLOMERULAR PODOCYTES
DIABETIC-NEPHROPATHY
SIGNALING PATHWAYS
3T3-L1 ADIPOCYTES
KIDNEY
MYH9
3122 Cancers
1182 Biochemistry, cell and molecular biology
Peer reviewed: Yes
Rights: cc_by_nc_nd
Usage restriction: openAccess
Self-archived version: publishedVersion


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