The small GTPase ADP-ribosylation factor 6 negatively regulates dendritic spine formation |
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Authors: | Miyazaki Hideyuki Yamazaki Masakazu Watanabe Hiroshi Maehama Tomohiko Yokozeki Takeaki Kanaho Yasunori |
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Affiliation: | Department of Physiological Chemistry, Graduate School of Comprehensive Sciences and Institute of Basic Medical Sciences, University of Tsukuba, 1-1-1 Ten-nohdai, Tsukuba 305-8575, Japan. |
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Abstract: | Actin cytoskeletal reorganization and membrane trafficking are important for spine morphogenesis. Here we investigated whether the small GTPase, ADP-ribosylation factor 6 (ARF6), which regulates actin dynamics and peripheral vesicular trafficking, is involved in the regulation of spine formation. The developmental expression pattern of ARF6 in mouse hippocampus was similar to that of the post-synaptic density protein-95, and these molecules colocalized in mouse hippocampal neurons. Overexpression of a constitutively active ARF6 mutant in cultured hippocampal neurons decreased the spine density, whereas a dominant-negative ARF6 mutant increased the density. These results demonstrate a novel function for ARF6 as a key regulator of spine formation. |
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Keywords: | ARF, ADP-ribosylation factor ARF CA, a constitutively active ARF mutant ARF DN, a dominant-negative ARF mutant MAP-2, microtubule-associated protein-2 PIP5K, phosphatidylinositol 4-phosphate 5-kinase PSD, post-synaptic density HA, hemagglutinin HRP, horseradish peroxidase DMEM, Dulbecco’s modified Eagle’s medium DIV, days in vitro BSA, bovine serum albumin FCS, fetal calf serum PBS, phosphate-buffered saline GEF, guanine nucleotide exchange factor P, postnatal days |
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