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J Neurochem. 2018 Dec;147(5):595-608. doi: 10.1111/jnc.14570. Epub 2018 Nov 20.

Adenomatous polyposis coli-stimulated GEF 1 (Asef1) is a negative regulator of excitatory synaptic function.

Author information

1
Graduate Program in Neuroscience, Department of Medicine and Microbiology, College of Medicine, Chungbuk National University, Cheongju, Korea.
2
Korea Brain Research Institute, Daegu, Korea.
3
Department of Pharmacology, Wonkwang University School of Medicine, Iksan, Korea.
4
Department of Neurosurgery, College of Medicine, Chungbuk National University, Cheongju, Korea.
5
Department of Medicine and Biochemistry, College of Medicine, Chungbuk National University, Cheongju, Korea.
6
Department of Physiology, Department of Biomedical Science, Seoul National University College of Medicine, Seoul, Korea.
7
Department of Biological Sciences, College of Natural Sciences, Seoul National University, Seoul, Korea.

Abstract

Guanine nucleotide exchange factors (GEFs) play important roles in many cellular processes, including regulation of the structural plasticity of dendritic spines. A GEF protein, adenomatous polyposis coli-stimulated GEF 1 (Asef1, ARHGEF4) is highly expressed in the nervous system. However, the function of Asef1 has not been investigated in neurons. Here, we present evidence showing that Asef1 negatively regulates the synaptic localization of postsynaptic density protein 95 (PSD-95) in the excitatory synapse by inhibiting Staufen-mediated synaptic localization of PSD-95. Accordingly, Asef1 expression impairs synaptic transmission in hippocampal cultured neurons. In addition, neuronal activity facilitates the dissociation of Asef1 from Staufen in a phosphoinositide 3 kinase (PI3K)-dependent manner. Taken together, our data reveal Asef1 functions as a negative regulator of synaptic localization of PSD-95 and synaptic transmission.

KEYWORDS:

Asef1; PSD-95; Staufen; dendritic plasticity; synaptic transmission

PMID:
30125942
DOI:
10.1111/jnc.14570

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