Annotated protein:	ADP-ribosylation factor 6 (EC 3.6.5.2). Gene symbol: ARF6. Taxonomy: Rattus norvegicus (Rat). Uniprot ID: P62332
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SynGO gene info:	SynGO data @ ARF6
Ontology domain:	Biological Process
SynGO term:	maintenance of postsynaptic density structure (GO:0099562)
Synapse type(s):	hippocampus, glutamatergic
Annotated paper:	Choi S, et al. "ARF6 and EFA6A regulate the development and maintenance of dendritic spines" J Neurosci. 2006 May 3;26(18):4811-9 PMID:16672654
Figure(s):	fig 2, 5, 6, 8
Annotation description:	ARF6 protects mature dendritic spines from tetrodotoxin (inactivity)-induced destabilization in cultured hippocampal neurons. 21/2/2018 Pim Fig.2: "ARF6 promotes spine formation" - "ARF6 T157A increased the linear density of dendritic spines (defined as dendritic protrusions of 0.4-3 μm in length with or without a head), with a concomitant decrease in the density of filopodia (defined as dendritic protrusions of 3-10 μm in length) and hence no change in the density of total dendritic protrusions (spine plus filopodia) (Fig. 2A-D). ARF6 T157A also decreased the length of dendritic protrusions (Fig. 2E,H) and increased the localization of PSD-95 in dendritic spines (Fig. 2G)." Fig.5: "Knockdown of EFA6A and ARF6 by siRNA results in a decrease in spine formation" - Knockdown of ARF6 in cultured neurons (DIV 13-16) led to a decrease in spine density, with a concomitant increase in filopodia density (Fig. 5A-D), probably because of a reduced filopodia-to-spine conversion...Knockdown of EFA6A also resulted in similar changes, although to a lesser extent in some parameters, compared with ARF6 knockdown (Fig. 5A-J)." Fig.6: "ARF6 is required for the conversion of filopodia to spines and stabilization of early spines" - " ARF6 knockdown markedly decreased the percentage of filopodia converted to spines (Fig. 6D), indicating that ARF6 is required for filopodia-to-spine conversion. When spines were monitored, ARF6 knockdown increased the percentage of spines disappeared but did not affect that converted to filopodia (Fig. 6E), indicating that ARF6 is required for the stabilization of early spines, in addition to filopodia-to-spine conversion." Fig.8: "ARF6 and EFA6A protect mature spines from destabilization." - "neurons expressing ARF6 T157A or EFA6A (DIV 17-20) were resistant to TTX-induced elongation of spines, with complete protection seen in ARF6 T157A (Fig. 8A-F). These results suggest that ARF6 and EFA6A may be involved in the stabilization of mature spines at the later stages." Note: EFA6A is shown to act via ARF6. ARF6 and EFA6A are shown to: "In support of this, overexpression of an active form of ARF6 (T157A) promotes spine formation even at an early stage (DIV 11), whereas siRNA knockdown of ARF6 suppresses it. Critically, our live imaging results demonstrate that ARF6 is required for the conversion of filopodia to spines and stabilization of early spines. Active ARF6 (T157A) also causes a decrease in protrusion length and increases in protrusion width and spine localization of PSD-95, all of which may reflect a morphological maturation accompanying filopodia-to-spine conversion. Conversely, siRNA knockdown of ARF6 results in increased protrusion length and decreased protrusion width and spine localization of PSD-95. Last, ARF6 protects mature spines from TTX-induced destabilization." - Together, these data point to a role in formation and maintenance of PSD's
Evidence tracking, Biological System:	Cultured neurons
Evidence tracking, Protein Targeting:	RNAi / shRNA Over-expression
Evidence tracking, Experiment Assay:	Confocal
Annotator(s):	Hwajin Jung (ORCID:0000-0001-6194-9648) Eunjoon Kim (ORCID:0000-0001-5518-6584)
Lab:	Center for Synaptic Brain Dysfunctions, Institute for Basic Science (IBS) and Department of Biological Sciences, Korea Advanced Institute of Science and Technology (KAIST), Daejeon 34141, South Korea
SynGO annotation ID:	2680
Dataset release (version):	20231201
View annotation as GO-CAM model: