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

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 IIA (NMHC-IIA; encoded by MYH9), a component of the nonmuscle myosin IIA (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. - Highlights: • Septinmore » 7, nonmuscle myosin heavy chain IIA (NMHC-IIA) and SNAP23 form a complex. • Knockdown of septin 7 increases NM-IIA activity in the SNAP23 complex. • Insulin decreases septin 7 level and increases NM-IIA activity in the SNAP23 complex. • Septin 7 hinders GSV docking/fusion by reducing NM-IIA activity in the SNAP23 complex.« less

Authors:
;  [1];  [2];  [3]; ; ;  [4];  [5];  [5];  [1];  [5];  [4];  [5];  [5];  [6];  [1]
  1. Department of Pathology, University of Helsinki, 00014 Helsinki (Finland)
  2. Department of Pathology, University of Helsinki and Helsinki University Hospital, 00290 Helsinki, 05850 Hyvinkää (Finland)
  3. Institute of Biotechnology, University of Helsinki, 00014 Helsinki (Finland)
  4. Folkhälsan Institute of Genetics, Folkhälsan Research Center, 00290 Helsinki (Finland)
  5. (Finland)
  6. (Australia)
Publication Date:
OSTI Identifier:
22649814
Resource Type:
Journal Article
Resource Relation:
Journal Name: Experimental Cell Research; Journal Volume: 350; Journal Issue: 2; Other Information: Copyright (c) 2016 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; Country of input: International Atomic Energy Agency (IAEA)
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES; CELL MEMBRANES; COMPLEXES; GLOMERULI; GLUCOSE; INSULIN; MYOSIN; PATIENTS; PHOSPHORYLATION; RATS; RECEPTORS; UPTAKE

Citation Formats

Wasik, Anita A., Dumont, Vincent, Tienari, Jukka, Nyman, Tuula A., Fogarty, Christopher L., Forsblom, Carol, Lehto, Markku, Abdominal Center Nephrology, University of Helsinki and Helsinki University Hospital, 000290 Helsinki, Diabetes&Obesity Research Program, Research Program´s Unit, 00014 University of Helsinki, Lehtonen, Eero, Laboratory Animal Centre, University of Helsinki, 00014 Helsinki, Groop, Per-Henrik, Abdominal Center Nephrology, University of Helsinki and Helsinki University Hospital, 000290 Helsinki, Diabetes&Obesity Research Program, Research Program´s Unit, 00014 University of Helsinki, Baker IDI Heart & Diabetes Institute, 3004 Melbourne, and Lehtonen, Sanna, E-mail: sanna.h.lehtonen@helsinki.fi. Septin 7 reduces nonmuscle myosin IIA activity in the SNAP23 complex and hinders GLUT4 storage vesicle docking and fusion. United States: N. p., 2017. Web. doi:10.1016/J.YEXCR.2016.12.010.
Wasik, Anita A., Dumont, Vincent, Tienari, Jukka, Nyman, Tuula A., Fogarty, Christopher L., Forsblom, Carol, Lehto, Markku, Abdominal Center Nephrology, University of Helsinki and Helsinki University Hospital, 000290 Helsinki, Diabetes&Obesity Research Program, Research Program´s Unit, 00014 University of Helsinki, Lehtonen, Eero, Laboratory Animal Centre, University of Helsinki, 00014 Helsinki, Groop, Per-Henrik, Abdominal Center Nephrology, University of Helsinki and Helsinki University Hospital, 000290 Helsinki, Diabetes&Obesity Research Program, Research Program´s Unit, 00014 University of Helsinki, Baker IDI Heart & Diabetes Institute, 3004 Melbourne, & Lehtonen, Sanna, E-mail: sanna.h.lehtonen@helsinki.fi. Septin 7 reduces nonmuscle myosin IIA activity in the SNAP23 complex and hinders GLUT4 storage vesicle docking and fusion. United States. doi:10.1016/J.YEXCR.2016.12.010.
Wasik, Anita A., Dumont, Vincent, Tienari, Jukka, Nyman, Tuula A., Fogarty, Christopher L., Forsblom, Carol, Lehto, Markku, Abdominal Center Nephrology, University of Helsinki and Helsinki University Hospital, 000290 Helsinki, Diabetes&Obesity Research Program, Research Program´s Unit, 00014 University of Helsinki, Lehtonen, Eero, Laboratory Animal Centre, University of Helsinki, 00014 Helsinki, Groop, Per-Henrik, Abdominal Center Nephrology, University of Helsinki and Helsinki University Hospital, 000290 Helsinki, Diabetes&Obesity Research Program, Research Program´s Unit, 00014 University of Helsinki, Baker IDI Heart & Diabetes Institute, 3004 Melbourne, and Lehtonen, Sanna, E-mail: sanna.h.lehtonen@helsinki.fi. Sun . "Septin 7 reduces nonmuscle myosin IIA activity in the SNAP23 complex and hinders GLUT4 storage vesicle docking and fusion". United States. doi:10.1016/J.YEXCR.2016.12.010.
@article{osti_22649814,
title = {Septin 7 reduces nonmuscle myosin IIA activity in the SNAP23 complex and hinders GLUT4 storage vesicle docking and fusion},
author = {Wasik, Anita A. and Dumont, Vincent and Tienari, Jukka and Nyman, Tuula A. and Fogarty, Christopher L. and Forsblom, Carol and Lehto, Markku and Abdominal Center Nephrology, University of Helsinki and Helsinki University Hospital, 000290 Helsinki and Diabetes&Obesity Research Program, Research Program´s Unit, 00014 University of Helsinki and Lehtonen, Eero and Laboratory Animal Centre, University of Helsinki, 00014 Helsinki and Groop, Per-Henrik and Abdominal Center Nephrology, University of Helsinki and Helsinki University Hospital, 000290 Helsinki and Diabetes&Obesity Research Program, Research Program´s Unit, 00014 University of Helsinki and Baker IDI Heart & Diabetes Institute, 3004 Melbourne and Lehtonen, Sanna, E-mail: sanna.h.lehtonen@helsinki.fi},
abstractNote = {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 IIA (NMHC-IIA; encoded by MYH9), a component of the nonmuscle myosin IIA (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. - Highlights: • Septin 7, nonmuscle myosin heavy chain IIA (NMHC-IIA) and SNAP23 form a complex. • Knockdown of septin 7 increases NM-IIA activity in the SNAP23 complex. • Insulin decreases septin 7 level and increases NM-IIA activity in the SNAP23 complex. • Septin 7 hinders GSV docking/fusion by reducing NM-IIA activity in the SNAP23 complex.},
doi = {10.1016/J.YEXCR.2016.12.010},
journal = {Experimental Cell Research},
number = 2,
volume = 350,
place = {United States},
year = {Sun Jan 15 00:00:00 EST 2017},
month = {Sun Jan 15 00:00:00 EST 2017}
}