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BMC Biochem. 2015 Apr 30;16:11. doi: 10.1186/s12858-015-0040-y.

Sigma-1 receptor directly interacts with Rac1-GTPase in the brain mitochondria.

Author information

1
Institute of Chemical Biology, Ilia State University, 3/5 Cholokashvili av, Tbilisi, 0162, Georgia. nino_natsvlishvili@iliauni.edu.ge.
2
Department of Biochemistry, I.Beritashvili Center of Experimental Biomedicine, 14 Gotua st, Tbilisi, 0160, Georgia. nino_natsvlishvili@iliauni.edu.ge.
3
Institute of Chemical Biology, Ilia State University, 3/5 Cholokashvili av, Tbilisi, 0162, Georgia. nino.goguadze.2@iliauni.edu.ge.
4
Institute of Chemical Biology, Ilia State University, 3/5 Cholokashvili av, Tbilisi, 0162, Georgia. elene_zhuravliova@iliauni.edu.ge.
5
Department of Biochemistry, I.Beritashvili Center of Experimental Biomedicine, 14 Gotua st, Tbilisi, 0160, Georgia. elene_zhuravliova@iliauni.edu.ge.
6
Institute of Chemical Biology, Ilia State University, 3/5 Cholokashvili av, Tbilisi, 0162, Georgia. davit_mikeladze@iliauni.edu.ge.
7
Department of Biochemistry, I.Beritashvili Center of Experimental Biomedicine, 14 Gotua st, Tbilisi, 0160, Georgia. davit_mikeladze@iliauni.edu.ge.

Abstract

BACKGROUND:

Small Rho-GTPases are critical mediators of neuronal plasticity and are involved in the pathogenesis of several psychiatric and neurological disorders. Rac-GTPase forms a multiprotein complex with upstream and downstream regulators that are essential for the spatiotemporal transmission of Rac signaling. The sigma-1 receptor (Sig1R) is a ligand-regulated membrane protein chaperone, and multiprotein complex assembly is essential to sigma-receptor function.

RESULTS:

Using immunoprecipitation techniques, we have shown that in mitochondrial membranes Sig1R could directly interact with Rac1. Besides Rac1, the Sig1R forms complexes with inositol 1,4,5-trisphosphate receptor and Bcl2, suggesting that mitochondrial associated membranes (MAM) are involved in this macromolecular complex formation. Assembly of this complex is ligand-specific and depends on the presence of sigma agonist/antagonist, as well as on the presence of GTP/GDP. Treatment of mitochondrial membranes with (+)-pentazocine leads to the (+)-pentazocine-sensitive phosphorylation of Bad and the pentazocine-sensitive NADPH-dependent production of ROS.

CONCLUSION:

We suggest that Sig1R through Rac1 signaling induces mild oxidative stress that possibly is involved in the regulation of neuroplasticity, as well as in the prevention of apoptosis and autophagy.

PMID:
25924612
PMCID:
PMC4430930
DOI:
10.1186/s12858-015-0040-y
[Indexed for MEDLINE]
Free PMC Article

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