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: University of Helsinki, Department of Pathology
University of Helsinki, Sanna Lehtonen research group
University of Helsinki, Department of Pathology
University of Helsinki, Institute of Biotechnology
University of Helsinki, Clinicum
University of Helsinki, Clinicum
University of Helsinki, Nefrologian yksikkö
University of Helsinki, Medicum
University of Helsinki, Clinicum
University of Helsinki, Medicum
Date: 2017-01-15
Language: eng
Number of pages: 13
Belongs to series: Experimental Cell Research
ISSN: 0014-4827
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
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