Arf6 regulates the cycling and the readily releasable pool of synaptic vesicles at hippocampal synapse

Tagliatti, Erica; Fadda, Manuela; Falace, Antonio; Benfenati, Fabio; Fassio, Anna

doi:10.7554/elife.10116

Cited by 54 publications

(54 citation statements)

References 43 publications

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“…In axons, ARF activation event may be spatially regulated, with initial activation occurring within the AIS, and subsequent activation maintained throughout the axon by ARNO. Axonal ARF activation may be necessary to aid neurotransmission, because ARF6 activation drives synaptic vesicles towards recycling rather than endosomal sorting, enabling maintenance of the readily releasable synaptic vesicle pool (Tagliatti et al, 2016).…”

Section: Discussionmentioning

confidence: 99%

EFA6 regulates selective polarised transport and axon regeneration from the axon initial segment

Eva

Koseki

Kanamarlapudi

et al. 2017

Preprint

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Summary Statement:We identify a novel resident of the axon initial segment, EFA6. This 14 functions to prevent growth-promoting molecules from entering mature CNS axons. 15Removing EFA6 elevates the axon's regenerative potential. carriers. We reasoned that this exclusion might contribute to the intrinsic inability of CNS 23 neurons to regenerate, and investigated this hypothesis using laser axotomy. We identify a 24 novel regulator of selective axon transport and regeneration, the ARF6 GEF EFA6. EFA6 25 exerts its effects from a previously unreported location within the axon initial segment (AIS). 26EFA6 does not localise here in DRG axons, and in these neurons, ARF activation is 27 counteracted by an ARF-GAP which is absent from the CNS, ACAP1. Depleting EFA6 from

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Section: Discussionmentioning

confidence: 99%

EFA6 regulates selective polarised transport and axon regeneration from the axon initial segment

Eva

Koseki

Kanamarlapudi

et al. 2017

Preprint

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“…Interestingly, cytohesin-1 has been shown to facilitate synaptic transmission in Xenopus laevis neuromuscular junction, most likely by making more presynaptic vesicles available for fusion at the plasma membrane through a direct interaction with Munc13-1 (also known as Unc13a) (Ashery et al, 1999;Neeb et al, 1999). By contrast, in hippocampal neurons, Arf6 silencing has recently been reported to increase synaptic exocytosis, and both Arf6 silencing and cytohesin inhibition by SecinH3 results in an increase in the number of docked synaptic vesicles (Tagliatti et al, 2016). As neuronal tau release appears to be related to plasma membrane fusion of presynaptic vesicles (Pooler et al, 2013;Yamada et al, 2014), it seems plausible that FRMD4A, cytohesin and Arf6 levels and activity in neurons serve as regulators of tau secretion.…”

Section: Discussionmentioning

confidence: 99%

FRMD4A–cytohesin signaling modulates the cellular release of tau

Nykänen

Brunello

et al. 2016

Journal of Cell Science

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One of the defining pathological features of Alzheimer's disease is the intraneuronal accumulation of tau (also known as MAPT) protein.Tau is also secreted from neurons in response to various stimuli and accumulates in the cerebrospinal fluid of Alzheimer's disease patients. Tau pathology might spread from cell to cell through a mechanism involving secretion and uptake. Here, we developed an assay to follow cellular release and uptake of tau dimers. Individual silencing of ten common late-onset Alzheimer's disease risk genes in HEK293T cells expressing the tau reporters suggested that FRMD4A is functionally linked to tau secretion. FRMD4A depletion by using RNA interference (RNAi) reduced and overexpression increased tau secretion. The activity of cytohesins, interactors of FRMD4A and guanine-nucleotide-exchange factors of Arf6, was necessary for FRMD4A-induced tau secretion. Increased Arf6 and cell polarity signaling through Par6 and atypical protein kinase Cζ (aPKCζ) stimulated tau secretion. In mature cortical neurons, FRMD4A RNAi or inhibition of cytohesins strongly upregulated secretion of endogenous tau. These results suggest that FRMD4A, a genetic risk factor for late-onset Alzheimer's disease, regulates tau secretion by activating cytohesin-Arf6 signaling. We conclude that genetic risk factors of Alzheimer's disease might modulate disease progression by altering tau secretion.

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“…In addition, vATPase itself may be able to recruit selected regulators of vesicular trafficking, like small GTPase ADP‐ribosylation factor 6 (Arf6) . Arf6 can regulate the size of the releasable pool of SVs and directly signal the retrieved SVs toward the next round of fusion …”

Section: Coordination Between Vesicle Acidification and Trafficking Amentioning

confidence: 99%

Regulation of synaptic vesicle acidification at the neuronal synapse

Gowrisankaran

Milošević

2020

IUBMB Life

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The vacuolar H+‐adenosine triphosphatases (vATPases) acidify multiple intracellular organelles, including synaptic vesicles (SVs) and secretory granules. Acidification of SVs represents a critical point during the SV cycle: without acidification, neurotransmitters cannot be loaded into SVs. Despite the obvious importance of the vesicle acidification process for neurotrasmission and the life of complex organisms, little is known about the regulation of vATPase at the neuronal synapse. In addition, the composition of the vATPase complex on the SVs is unclear. Here, we summarize the key features of vATPase found on SVs, and propose a model of how vATPase activity is regulated during the SV cycle. It is anticipated that the information from the SV lumen is communicated to SV surface in order to signal successful acidification and neurotransmitter loading: we postulate here that the regulators of the vATPase activity exist (e.g., Rabconnectin‐3) that promote the recruitment of SV peripheral proteins and, consequently, SV fusion.

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Arf6 regulates the cycling and the readily releasable pool of synaptic vesicles at hippocampal synapse

Cited by 54 publications

References 43 publications

EFA6 regulates selective polarised transport and axon regeneration from the axon initial segment

EFA6 regulates selective polarised transport and axon regeneration from the axon initial segment

FRMD4A–cytohesin signaling modulates the cellular release of tau

Regulation of synaptic vesicle acidification at the neuronal synapse

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