A presynaptic endosomal trafficking pathway controls synaptic growth signaling

Rodal, Avital A.; Blunk, Aline D.; Akbergenova, Yulia; Jorquera, Ramón A.; Buhl, Lauren Kaye; Littleton, J Troy

doi:10.1083/jcb.201009052

Cited by 86 publications

(148 citation statements)

References 60 publications

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“…Until now, Nwk has been thought to only constrain (rather than promote) synaptic growth, by regulating the traffic of growth factor receptors (19,20,23). Our present results suggest that Nwk plays a previously unrecognized role, downstream of its function in constraining signaling, to drive membrane remodeling, synaptopod formation, and growth of new boutons.…”

Section: Discussionsupporting

confidence: 54%

“…Interestingly, interactions between the F-BAR domain of the murine Nwk homolog FCHSD1 and the SH3 domain of SNX9 are associated with enhanced activation of WASp in vitro (21), although it is not clear whether this is the result of release of FCHSD1 autoinhibition or FCHSD1 activation of SNX9-WASp interactions. Clearly, further work is needed to identify which of a growing number of Nwk ligands are involved in the release from autoinhibition, and how they accomplish this effect (19,20,23).…”

Section: Discussionmentioning

confidence: 99%

“…The Nwk F-BAR domain forms a dimer that assembles into higher-order zigzag arrays on negatively charged membranes and promotes the formation of membrane ridges and scallops (17). Nwk is required at the Drosophila larval neuromuscular junction (NMJ) to constrain the traffic and signaling activity of growth factor receptors (18)(19)(20). Mammalian genomes encode two Nwk family members, FCHSD1 and FCHSD2, which are associated with stereocilia and the trafficking of neurotransmitter receptors (21,22).…”

mentioning

confidence: 99%

“…Mammalian genomes encode two Nwk family members, FCHSD1 and FCHSD2, which are associated with stereocilia and the trafficking of neurotransmitter receptors (21,22). Nwk interacts with WASp and dynamin via its SH3a domain (19,20), and cooperates with Cdc42 to activate WASp/Arp2/3-mediated actin polymerization (20). We previously showed that both SH3 domains of Nwk bind directly to the Nwk F-BAR domain in solution via electrostatic interactions, shifting the lipid charge requirements for Nwk-induced membrane deformation (16).…”

mentioning

confidence: 99%

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Coordinated autoinhibition of F-BAR domain membrane binding and WASp activation by Nervous Wreck

Stanishneva‐Konovalova

Kelley

Eskin

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

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Membrane remodeling by Fes/Cip4 homology-Bin/Amphiphysin/Rvs167 (F-BAR) proteins is regulated by autoinhibitory interactions between their SRC homology 3 (SH3) and F-BAR domains. The structural basis of autoregulation, and whether it affects interactions of SH3 domains with other cellular ligands, remain unclear. Here we used single-particle electron microscopy to determine the structure of the F-BAR protein Nervous Wreck (Nwk) in both soluble and membrane-bound states. On membrane binding, Nwk SH3 domains do not completely dissociate from the F-BAR dimer, but instead shift from its concave surface to positions on either side of the dimer. Unexpectedly, along with controlling membrane binding, these autoregulatory interactions inhibit the ability of Nwk-SH3a to activate Wiskott–Aldrich syndrome protein (WASp)/actin related protein (Arp) 2/3-dependent actin filament assembly. In Drosophila neurons, Nwk autoregulation restricts SH3a domain-dependent synaptopod formation, synaptic growth, and actin organization. Our results define structural rearrangements in Nwk that control F-BAR–membrane interactions as well as SH3 domain activities, and suggest that these two functions are tightly coordinated in vitro and in vivo.

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Section: Discussionsupporting

confidence: 54%

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

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Coordinated autoinhibition of F-BAR domain membrane binding and WASp activation by Nervous Wreck

Stanishneva‐Konovalova

Kelley

Eskin

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

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“…57,58 Drosophila Nwk proteins correspondingly recruit WASP, 59 Dynamin, 60 and sorting nexin Snx16 61 in neurons to regulate synaptic growth receptor signaling at presynaptic neuromuscular junctions. 61,62 Therefore, multiple F-BAR proteins at endocytic sites in different cell types build branched actin networks through recruitment of WASP or WAVE, and assist in vesicle scission through recruitment of Dynamin.…”

Section: Scaffolding Functionsmentioning

confidence: 99%

Linking up at the BAR: Oligomerization and F-BAR protein function

McDonald

Gould

2016

Cell Cycle

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As cells grow, move, and divide, they must reorganize and rearrange their membranes and cytoskeleton. The F-BAR protein family links cellular membranes with actin cytoskeletal rearrangements in processes including endocytosis, cytokinesis, and cell motility. Here we review emerging information on mechanisms of F-BAR domain oligomerization and membrane binding, and how these activities are coordinated with additional domains to accomplish scaffolding and signaling functions.

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Transcription factor Sp4 regulates expression of nervous wreck 2 to control NMDAR1 levels and dendrite patterning

Sun

Pinacho

Saia

et al. 2014

Developmental Neurobiology

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Glutamatergic signaling through N-methyl-D-aspartate receptors (NMDARs) is important for neuronal development and plasticity and is often dysregulated in psychiatric disorders. Mice mutant for the transcription factor Sp4 have reduced levels of NMDAR subunit 1 (NR1) protein, but not mRNA, and exhibit behavioral and memory deficits (Zhou et al., 2010). In developing cerebellar granule neurons (CGNs), Sp4 controls dendrite patterning (Ramos et al., 2007). Sp4 target genes that regulate dendrite pruning or NR1 levels are not known. Here we report that Sp4 activates transcription of Nervous Wreck 2 (Nwk2; also known as Fchsd1) and, further, that Nwk2, an F-BAR-domain containing protein, mediates Sp4-dependent regulation of dendrite patterning and cell surface expression of NR1. Knockdown of Nwk2 in CGNs increased primary dendrite number, phenocopying Sp4 knockdown, and exogenous expression of Nwk2 in Sp4-depleted neurons rescued dendrite number. We observed that acute Sp4 depletion reduced levels of surface, but not total, NR1, and this was rescued by Nwk2 expression. Furthermore, expression of Nr1 suppressed the increase in dendrite number in Sp4- or Nwk2-depleted neurons. We previously reported that Sp4 protein levels were reduced in cerebellum of subjects with bipolar disorder (BD) (Pinacho et al., 2011). Here we report that Nwk2 mRNA and NR1 protein levels were also reduced in postmortem cerebellum of BD subjects. Our data suggest a role for Sp4-regulated Nwk2 in NMDAR trafficking and identify an Sp4-Nwk2-NMDAR1 pathway that regulates neuronal morphogenesis during development and may be disrupted in bipolar disorder.

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A presynaptic endosomal trafficking pathway controls synaptic growth signaling

Abstract: Association of Nwk with SNX16 promotes down-regulation of synaptic growth signaling at the interface between early and recycling endosomes.

Cited by 86 publications

References 60 publications

Coordinated autoinhibition of F-BAR domain membrane binding and WASp activation by Nervous Wreck

Coordinated autoinhibition of F-BAR domain membrane binding and WASp activation by Nervous Wreck

Linking up at the BAR: Oligomerization and F-BAR protein function

Transcription factor Sp4 regulates expression of nervous wreck 2 to control NMDAR1 levels and dendrite patterning

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