Physiological functions of the small GTPase Arf6 in the nervous system

Akiyama, Masahiro; Kanaho, Yasunori

doi:10.1080/21541248.2015.1043041

Cited by 5 publications

(4 citation statements)

References 52 publications

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“…ARF6 is a key intracellular trafficking regulator for endocytosis, exocytosis, endosomal recycling, and cytokinesis through the reorganization of the actin cytoskeleton (33). ARF6 plays substantial roles in axonal outgrowth, dendritic branching, and spine formation (5) and may be related to disorders such as memory impairment and mental disorder (34). However, these reports were attained from in vitro surveys and there are a few in vivo examinations about the physiological role of this protein in the CNS.…”

Section: Discussionmentioning

confidence: 99%

Exercise Training Enhances Expression of Tropomedulin-2 and ADP-Ribosylation Factor 6 in the Cerebellum of Male Wistar Rats

Taherabadi

Rahmati

2019

Zahedan J Res Med Sci

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Background: It has been well documented that exercise training (ET) induces beneficial effects on the central nervous system (CNS); however, the underlying mechanisms are less known. We presumed that actin cytoskeleton regulatory proteins such as ADPribosylation factors 6 (ARF6) and tropomodulin 2 (TMOD2) may be important elements of Exercise-Induced Neuroplasticity (EIN). We evaluated this hypothesis in the present study. Methods: We randomly divided 12 male Wistar rats into control (C) and training (T) groups. The T group was exposed to six weeks of moderate-intensity treadmill running. The ARF6 and TMOD2 gene and protein expressions in the cerebellum of male Wistar rats were assessed by the real-time PCR and western blot analysis. Results: The results showed that TMOD2 and ARF6 gene and protein expressions were significantly higher in the T group than in the C group. Conclusions: It seems that chronic treadmill running increases TMOD2 and ARF6 gene and protein expressions in the cerebellum and these changes probably lead to the improvement of brain function.

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Section: Discussionmentioning

confidence: 99%

Exercise Training Enhances Expression of Tropomedulin-2 and ADP-Ribosylation Factor 6 in the Cerebellum of Male Wistar Rats

Taherabadi

Rahmati

2019

Zahedan J Res Med Sci

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“…Indeed, specific lack of ARF6 in rodent neurons resulted in a reduced size of the corpus callosum and of the hippocampal fimbria, underlying impaired secretion of the guidance factor FGF2. This results in defective oligodendrocytes migration and thereby axonal myelination (Akiyama and Kanaho, 2015). Moreover, experiments in mice models of KIF16B loss of function, which recapitulate FGFR2 KO animals, demonstrate that a KINESIN/RAB14 complex mediates Golgi-to-endosome trafficking of the FGFR and that this is crucial for epiblast development (Ueno et al, 2011).…”

Section: Fgf Egf and Vegf Signalingmentioning

confidence: 99%

In vivo Functional Genomics for Undiagnosed Patients: The Impact of Small GTPases Signaling Dysregulation at Pan-Embryo Developmental Scale

Lauri

Fasano

Venditti

et al. 2021

Front. Cell Dev. Biol.

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While individually rare, disorders affecting development collectively represent a substantial clinical, psychological, and socioeconomic burden to patients, families, and society. Insights into the molecular mechanisms underlying these disorders are required to speed up diagnosis, improve counseling, and optimize management toward targeted therapies. Genome sequencing is now unveiling previously unexplored genetic variations in undiagnosed patients, which require functional validation and mechanistic understanding, particularly when dealing with novel nosologic entities. Functional perturbations of key regulators acting on signals’ intersections of evolutionarily conserved pathways in these pathological conditions hinder the fine balance between various developmental inputs governing morphogenesis and homeostasis. However, the distinct mechanisms by which these hubs orchestrate pathways to ensure the developmental coordinates are poorly understood. Integrative functional genomics implementing quantitative in vivo models of embryogenesis with subcellular precision in whole organisms contribute to answering these questions. Here, we review the current knowledge on genes and mechanisms critically involved in developmental syndromes and pediatric cancers, revealed by genomic sequencing and in vivo models such as insects, worms and fish. We focus on the monomeric GTPases of the RAS superfamily and their influence on crucial developmental signals and processes. We next discuss the effectiveness of exponentially growing functional assays employing tractable models to identify regulatory crossroads. Unprecedented sophistications are now possible in zebrafish, i.e., genome editing with single-nucleotide precision, nanoimaging, highly resolved recording of multiple small molecules activity, and simultaneous monitoring of brain circuits and complex behavioral response. These assets permit accurate real-time reporting of dynamic small GTPases-controlled processes in entire organisms, owning the potential to tackle rare disease mechanisms.

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“…The ADP-ribosylation factor 6 (Arf6) is a guanosine-5'triphosphate (GTP)-binding protein with many functions such as actin cytoskeleton regulation, cell morphology and polarity, signal transduction, membrane traffic, endocytosis, and exocytosis (5). However, the roles of Arf6 in DPN are not explored yet.…”

Section: Objectivesmentioning

confidence: 99%

Effect of Endurance Training on Cerebellar Gene Expression of the ADP-Ribosylation Factor 6 in Rats with Diabetic Peripheral Neuropathy

Taherabadi

Rahmati

Mirnasuri

2019

Zahedan J Res Med Sci

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Background: Experimental evidence demonstrated that endurance training (ET) could be beneficial for the diabetic peripheral neuropathy (DPN), but its mechanism is not clear. Due to the critical role of the ADP-ribosylation factor (Arf6) in the nervous system, the current study aimed at evaluating the effects of ET on gene expression of Arf6 in cerebellum of male Wistar rats with DPN. Methods: Animals were randomly divided into three groups: Control (C), diabetic control (DC), and diabetic trained (DT). Diabetes induction was performed by a single intraperitoneal injection of streptozotocin (STZ). Behavioral nociception assessment was conducted by Von Frey filaments and tail flick tests. Treadmill protocol consisted of six weeks of moderate intensity endurance training. The Arf6 cerebellar gene expression was assessed by the real-time PCR.Results: In the current study, the Arf6 gene expression levels in the DC group were significantly higher than those of the C group (P = 0.003). Also, ET could damp this elevation in diabetic rats (P = 0.004). Conclusions: It seems that Arf6 is an important mediator of stress-induced plasticity in the nervous system in response to ET and neurodegeneration disease, but the exact physiological functions of Arf6 are not clear. Hence, further studies are required to identify these issues.

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Physiological functions of the small GTPase Arf6 in the nervous system

Cited by 5 publications

References 52 publications

Exercise Training Enhances Expression of Tropomedulin-2 and ADP-Ribosylation Factor 6 in the Cerebellum of Male Wistar Rats

Exercise Training Enhances Expression of Tropomedulin-2 and ADP-Ribosylation Factor 6 in the Cerebellum of Male Wistar Rats

In vivo Functional Genomics for Undiagnosed Patients: The Impact of Small GTPases Signaling Dysregulation at Pan-Embryo Developmental Scale

Effect of Endurance Training on Cerebellar Gene Expression of the ADP-Ribosylation Factor 6 in Rats with Diabetic Peripheral Neuropathy

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