SynArfGEF is a guanine nucleotide exchange factor for Arf6 and localizes preferentially at post-synaptic specializations of inhibitory synapses

Fukaya, M., Kamata, A., Hara, Y., Tamaki, H., Katsumata, O., Ito, N., Takeda, S., Hata, Y., Suzuki, T., Watanabe, M., Harvey, R.J. and Sakagami, H. (2011) SynArfGEF is a guanine nucleotide exchange factor for Arf6 and localizes preferentially at post-synaptic specializations of inhibitory synapses. Journal of Neurochemistry, 116 (6). pp. 1122-1137. 10.1111/j.1471-4159.2010.07167.x.

Full text available as:

[img]PDF - Accepted Version
4060Kb

DOI: 10.1111/j.1471-4159.2010.07167.x

Abstract

SynArfGEF, also known as BRAG3 or IQSEC3, is a member of the brefeldin A-resistant Arf-GEF/IQSEC family and was originally identified by screening for mRNA species associated with the post-synaptic density fraction. In this study, we demonstrate that synArfGEF activates Arf6, using Arf pull down and transferrin incorporation assays. Immunohistochemical analysis reveals that synArfGEF is present in somata and dendrites as puncta in close association with inhibitory synapses, whereas immunoelectron microscopic analysis reveals that synArfGEF localizes preferentially at post-synaptic specializations of symmetric synapses. Using yeast two-hybrid and pull down assays, we show that synArfGEF is able to bind utrophin/dystrophin and S-SCAM/MAGI-2 scaffolding proteins that localize at inhibitory synapses. Double immunostaining reveals that synArfGEF co-localizes with dystrophin and S-SCAM in cultured hippocampal neurons and cerebellar cortex, respectively. Both β-dystroglycan and S-SCAM were immunoprecipitated from brain lysates using anti-synArfGEF IgG. Taken together, these findings suggest that synArfGEF functions as a novel regulator of Arf6 at inhibitory synapses and associates with the dystrophin-associated glycoprotein complex and S-SCAM.

Item Type:Article
Uncontrolled Keywords:ADP-ribosylation factor 6;dystrophin;gephyrin;PDZ domain;post-synaptic density
Departments, units and centres:Department of Pharmacology > Department of Pharmacology
ID Code:2294
Journal or Publication Title:Journal of Neurochemistry
Deposited By:Library Staff
Deposited On:06 Oct 2011 10:26
Last Modified:06 Oct 2011 10:26

Repository Staff Only: Item control page

School of Pharmacy Staff Only: Edit a copy to replace this item