ACAP3 regulates neurite outgrowth through its GAP activity specific to Arf6 in mouse hippocampal neurons

Miura, Yuki; Hongu, Tsunaki; Yamauchi, Yohei; Funakoshi, Yuji; Katagiri, Naohiro; Ohbayashi, Norihiko; Kanaho, Yasunori

doi:10.1042/bcj20160183

Cited by 20 publications

(18 citation statements)

References 46 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Among the hubs in this module, Actn1 , Fkbp8 and Acap3 are involved in neurite extension . In particular, hippocampal neurons have shown abolished neurite outgrowth after Acap3 knockdown ( Miura et al, 2016 ). Other hubs were Cacnb3 , a voltage-activated calcium channel, and the immune-related genes Cnrip and Il16 .…”

Section: Resultsmentioning

confidence: 99%

Temporal analysis of hippocampal CA3 gene coexpression networks in a rat model of febrile seizures

Azevedo

Khaled

Santos

et al. 2018

Disease Models &Amp; Mechanisms

View full text Add to dashboard Cite

Complex febrile seizures during infancy constitute an important risk factor for development of epilepsy. However, little is known about the alterations induced by febrile seizures that make the brain susceptible to epileptic activity. In this context, the use of animal models of hyperthermic seizures (HS) could allow the temporal analysis of brain molecular changes that arise after febrile seizures. Here, we investigated temporal changes in hippocampal gene coexpression networks during the development of rats submitted to HS. Total RNA samples were obtained from the ventral hippocampal CA3 region at four time points after HS at postnatal day (P) 11 and later used for gene expression profiling. Temporal endpoints were selected for investigating the acute (P12), latent (P30 and P60) and chronic (P120) stages of the HS model. A weighted gene coexpression network analysis was used to characterize modules of coexpressed genes, as these modules might contain genes with similar functions. The transcriptome analysis pipeline consisted of building gene coexpression networks, identifying network modules and hubs, performing gene-trait correlations and examining changes in module connectivity. Modules were functionally enriched to identify functions associated with HS. Our data showed that HS induce changes in developmental, cell adhesion and immune pathways, such as Wnt, Hippo, Notch, Jak-Stat and Mapk. Interestingly, modules involved in cell adhesion, neuronal differentiation and synaptic transmission were activated as early as 1 day after HS. These results suggest that HS trigger transcriptional alterations that could lead to persistent neurogenesis, tissue remodeling and inflammation in the CA3 hippocampus, making the brain prone to epileptic activity.

show abstract

Section: Resultsmentioning

confidence: 99%

Temporal analysis of hippocampal CA3 gene coexpression networks in a rat model of febrile seizures

Azevedo

Khaled

Santos

et al. 2018

Disease Models &Amp; Mechanisms

View full text Add to dashboard Cite

show abstract

“…Miura et al . () demonstrated that total neurite length, but not total neurite number, was significantly decreased in cultured hippocampal neurons transfected with shRNA for Arf6 or prepared from Arf6 knockout mice. Therefore, the opposite effects of knockdown between pallidin and cytohesin‐2 on total dendritic length can lead to the speculation that the interaction of pallidin with cytohesin‐2 may negatively regulate the stimulatory effect of the cytohesin‐2‐Arf pathway on dendritic extension by suppressing the GEF activity of cytohesin‐2 toward Arf6.…”

Section: Discussionmentioning

confidence: 98%

Pallidin is a novel interacting protein for cytohesin‐2 and regulates the early endosomal pathway and dendritic formation in neurons

Ito

Fukaya

Saegusa

et al. 2018

Journal of Neurochemistry

View full text Add to dashboard Cite

Cytohesin-2 is a member of the guanine nucleotide exchange factors for ADP ribosylation factor 1 (Arf1) and Arf6, which are small GTPases that regulate membrane traffic and actin dynamics. In this study, we first demonstrated that cytohesin-2 localized to the plasma membrane and vesicles in various subcellular compartment in hippocampal neurons by immunoelectron microscopy. Next, to understand the molecular network of cytohesin-2 in neurons, we conducted yeast two-hybrid screening of brain cDNA libraries using cytohesin-2 as bait and isolated pallidin, a component of the biogenesis of lysosome-related organelles complex 1 (BLOC-1) involved in endosomal trafficking. Pallidin interacted specifically with cytohesin-2 among cytohesin family members. Glutathione S-transferase pull-down and immunoprecipitation assays further confirmed the formation of a protein complex between cytohesin-2 and pallidin. Immunofluorescence demonstrated that cytohesin-2 and pallidin partially colocalized in various subsets of endosomes immunopositive for EEA1, syntaxin 12, and LAMP2 in hippocampal neurons. Knockdown of pallidin or cytohesin-2 reduced cytoplasmic EEA1-positive early endosomes. Furthermore, knockdown of pallidin increased the total dendritic length of cultured hippocampal neurons, which was rescued by co-expression of wild-type pallidin but not a mutant lacking the ability to interact with cytohesin-2. In contrast, knockdown of cytohesin-2 had the opposite effect on total dendritic length. The present results suggested that the interaction between pallidin and cytohesin-2 may participate in various neuronal functions such as endosomal trafficking and dendritic formation in hippocampal neurons. Cover Image for this issue: doi: 10.1111/jnc.14197.

show abstract

“…In mammalian cells, overexpression of ArfGAP1 produces more vesicles, rather than inhibiting transport [19]. The depletion of ACAP3, the ArfGAP for Arf6, resulted in the inhibition of neurite outgrowth [32]. Although Arf6•GTP levels increased by depletion of ACAP3, the shRNA of Arf6 also decreased neurite outgrowth.…”

Section: Arfgaps; Depletion or Overexpression?mentioning

confidence: 98%

ArfGAPs; Depletion or Overexpression?

Shiba¹

2017

Res Rev Insights

View full text Add to dashboard Cite

Arf proteins are small GTP binding proteins that regulate intracellular traffic, actin remodeling and lipid metabolism. In the GTP-bound state, Arf is thought to be an active form that can bind to organelle membranes and many effectors. Arf in the GDP-bound state is thought to be an inactive form and released to cytosol. Arf GTPase Activating Proteins (ArfGAPs) hydrolyze Arf•GTP to Arf·GTP. Because GAPs "inactivate" small GTPases, the research of GAPs has often been done by overexpression of the GAPs looking at the biological consequences of the overexpression. However, decades of study about ArfGAP1 in COPI coated vesicle formation has led to a molecular model by which ArfGAP1 plays a role in fidelity of cargo sorting. This model implies that a deletion experiment would be appropriate to analyze the function of ArfGAP family proteins, rather than overexpression. Here, I briefly describe the role of ArfGAP1 in COPI coated vesicle formation, and discuss the biological consequences of depletion of ArfGAPs.

show abstract

ACAP3 regulates neurite outgrowth through its GAP activity specific to Arf6 in mouse hippocampal neurons

Cited by 20 publications

References 46 publications

Temporal analysis of hippocampal CA3 gene coexpression networks in a rat model of febrile seizures

Temporal analysis of hippocampal CA3 gene coexpression networks in a rat model of febrile seizures

Pallidin is a novel interacting protein for cytohesin‐2 and regulates the early endosomal pathway and dendritic formation in neurons

ArfGAPs; Depletion or Overexpression?

Contact Info

Product

Resources

About