A Wnt-planar polarity pathway instructs neurite branching by restricting F-actin assembly through endosomal signaling

Chen, Chun‐Hao; He, Chun-Wei; Liao, Chien-Po; Pan, Chih-Hong

doi:10.1371/journal.pgen.1006720

Cited by 33 publications

(35 citation statements)

References 55 publications

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“…The frequency of actin trails is 5 ± 0.42/100 μm/minute (Figure S2F) and their velocity of extension is 0.42 ± 0.02 μm/s (Figure S2G). We also used Coronin‐1::mCherry (COR‐1), an orthologue of a mammalian actin‐binding protein associated predominantly with F‐actin, that is also known to cross‐link actin and microtubules in yeast . About half of the utCH‐rich regions are enriched with COR‐1 as well (Figure S3A,B).…”

Section: Resultsmentioning

confidence: 99%

Cargo crowding at actin‐rich regions along axons causes local traffic jams

Sood

Murthy

Kumar

et al. 2018

Traffic

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Steady axonal cargo flow is central to the functioning of healthy neurons. However, a substantial fraction of cargo in axons remains stationary up to several minutes. We examine the transport of precursors of synaptic vesicles (pre-SVs), endosomes and mitochondria in Caenorhabditis elegans touch receptor neurons, showing that stationary cargo are predominantly present at actin-rich regions along the neuronal process. Stationary vesicles at actin-rich regions increase the propensity of moving vesicles to stall at the same location, resulting in traffic jams arising from physical crowding. Such local traffic jams at actin-rich regions are likely to be a general feature of axonal transport since they also occur in Drosophila neurons. Repeated touch stimulation of C. elegans reduces the density of stationary pre-SVs, indicating that these traffic jams can act as both sources and sinks of vesicles. This suggests that vesicles trapped in actin-rich regions are functional reservoirs that may contribute to maintaining robust cargo flow in the neuron. A video abstract of this article can be found at: Video S1; Video S2.

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Section: Resultsmentioning

confidence: 99%

Cargo crowding at actin‐rich regions along axons causes local traffic jams

Sood

Murthy

Kumar

et al. 2018

Traffic

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“…Aliceblue was also significantly enriched for the syndecan-2 signaling pathway, and contained the SDC2 gene itself, which functions in dendritic structural changes together with F-actin [48]. Additionally, the most significant enrichment group unique to Cadetblue was the Wnt signaling pathway, which also regulates actin function [49, 50]. Of note, a prior study has shown that ARRB2 (a Cadetblue hub gene and member of Wnt signaling pathway) knockout rats display significantly decreased levels of voluntary ethanol consumption and psychomotor stimulation in response to ethanol [51].…”

Section: Discussionmentioning

confidence: 99%

Cross-species alcohol dependence-associated gene networks: Co-analysis of mouse brain gene expression and human genome-wide association data

Mignogna

Bacanu

Riley

et al. 2018

Preprint

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22Genome-wide association studies on alcohol dependence, by themselves, have yet to account for 23 the estimated heritability of the disorder and provide incomplete mechanistic understanding of 24 this complex trait. Integrating brain ethanol-responsive gene expression networks from model 25 organisms with human genetic data on alcohol dependence could aid in identifying dependence-26 associated genes and functional networks in which they are involved. This study used a 27 modification of the Edge-Weighted Dense Module Searching for genome-wide association 28 studies (EW-dmGWAS) approach to co-analyze whole-genome gene expression data from 29 ethanol-exposed mouse brain tissue, human protein-protein interaction databases and alcohol 30 dependence-related genome-wide association studies. Results revealed novel ethanol-regulated 31 and alcohol dependence-associated gene networks in prefrontal cortex, nucleus accumbens, and 32 ventral tegmental area. Three of these networks were overrepresented with genome-wide 33 association signals from an independent dataset. These networks were significantly 34 overrepresented for gene ontology categories involving several mechanisms, including actin 35 filament-based activity, transcript regulation, Wnt and Syndecan-mediated signaling, and 36 ubiquitination. Together, these studies provide novel insight for brain mechanisms contributing

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“…The PLM synaptic branches are formed in a stereotypical position along the main axon shaft. This is controlled by Wnt-Frizzled and Planar Cell Polarity signalling pathways that function to spatially restrict the focal accumulation of filamentous (F-) actin [40]. To examine whether MEC-17 is important for developmental patterning of the branch, we calculated the relative position of the branch to the cell body and axon terminus.…”

Section: Misregulation Of Mec-17 Disrupts Synaptic Branch Developmentmentioning

confidence: 99%

Development and maintenance of synaptic structure is mediated by the alpha-tubulin acetyltransferase MEC-17/αTAT1

Teoh

Wang

Chandhok

et al. 2019

Preprint

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Microtubules are fundamental elements of neuronal structure and function. They are dynamic structures formed from protofilament chains of α-and β-tubulin heterodimers. Acetylation of the lysine 40 (K40) residue of α-tubulin protects microtubules from mechanical stresses by imparting structural elasticity. The enzyme responsible for this acetylation event is MEC-17/αTAT1. However, despite its functional importance, the consequences of MEC-17/αTAT1 misregulation on neuronal structure and function are incompletely defined. Using overexpression and loss of function approaches, we have analysed the effects of MEC-17 misregulation on the development and maintenance of synaptic branches in the mechanosensory neurons of Caenorhabditis elegans. We find that synaptic branch extension is delayed, and that synaptogenesis is defective in these animals. Strikingly, by adulthood the synaptic branches specifically and spontaneously degenerate. This phenotype is dependent on the acetyltransferase domain on MEC-17, revealing that correct levels of K40 acetylation are essential for the maintenance of neuronal structure. Finally, we investigate the genetic pathways in which mec-17 functions, uncovering novel interactions with dual leucine-zipper kinase dlk-1 and the focal adhesion gene zyx-1/Zyxin. These interactions link MEC-17 together with factors involved in neuronal and actin remodelling to protect synaptic branches. Together, our results reveal that appropriate levels of α-tubulin K40 acetylation by MEC-17 are crucial for the development and maintenance of neuronal architecture.

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A Wnt-planar polarity pathway instructs neurite branching by restricting F-actin assembly through endosomal signaling

Cited by 33 publications

References 55 publications

Cargo crowding at actin‐rich regions along axons causes local traffic jams

Cargo crowding at actin‐rich regions along axons causes local traffic jams

Cross-species alcohol dependence-associated gene networks: Co-analysis of mouse brain gene expression and human genome-wide association data

Development and maintenance of synaptic structure is mediated by the alpha-tubulin acetyltransferase MEC-17/αTAT1

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