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

Journal Article · Sun Jan 15 04:00:00 EST 2017 · Experimental Cell Research

DOI:https://doi.org/10.1016/J.YEXCR.2016.12.010· OSTI ID:22649814

Wasik, Anita A.; Dumont, Vincent ^[1]; Tienari, Jukka ^[2]; Nyman, Tuula A. ^[3]; Fogarty, Christopher L.; Forsblom, Carol; Lehto, Markku ^[4]; Lehtonen, Eero ^[1]; Groop, Per-Henrik ^[4]; Lehtonen, Sanna ^[1]

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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)

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.

• OSTI ID: 22649814
• Journal Information: Experimental Cell Research, Journal Name: Experimental Cell Research Journal Issue: 2 Vol. 350; ISSN 0014-4827; ISSN ECREAL
• Country of Publication: United States
• Language: English

Related Subjects

60 APPLIED LIFE SCIENCES
CELL MEMBRANES
COMPLEXES
GLOMERULI
GLUCOSE
INSULIN
MYOSIN
PATIENTS
PHOSPHORYLATION
RATS
RECEPTORS
UPTAKE