Show simple item record

Actin assembly and non-muscle myosin activity drive dendrite retraction in an UNC-6/Netrin dependent self-avoidance response

dc.contributor.authorSundararajan, Lakshmi
dc.contributor.authorSmith, Cody J.
dc.contributor.authorWatson, Joseph D.
dc.contributor.authorMillis, Bryan A.
dc.contributor.authorTyska, Matthew J.
dc.contributor.authorMiller, David M.
dc.identifier.citationSundararajan L, Smith CJ, Watson JD, Millis BA, Tyska MJ, Miller DM, III (2019) Actin assembly and non-muscle myosin activity drive dendrite retraction in an UNC-6/Netrin dependent self-avoidance response. PLoS Genet 15(6): e1008228. pgen.1008228en_US
dc.description.abstractDendrite growth is constrained by a self-avoidance response that induces retraction but the downstream pathways that balance these opposing mechanisms are unknown. We have proposed that the diffusible cue UNC-6(Netrin) is captured by UNC-40(DCC) for a short-range interaction with UNC-5 to trigger self-avoidance in the C. elegans PVD neuron. Here we report that the actin-polymerizing proteins UNC-34(Ena/VASP), WSP-1(WASP), UNC-73(Trio), MIG-10(Lamellipodin) and the Arp2/3 complex effect dendrite retraction in the self-avoidance response mediated by UNC-6(Netrin). The paradoxical idea that actin polymerization results in shorter rather than longer dendrites is explained by our finding that NMY-1 (non-muscle myosin II) is necessary for retraction and could therefore mediate this effect in a contractile mechanism. Our results also show that dendrite length is determined by the antagonistic effects on the actin cytoskeleton of separate sets of effectors for retraction mediated by UNC-6(Netrin) versus outgrowth promoted by the DMA-1 receptor. Thus, our findings suggest that the dendrite length depends on an intrinsic mechanism that balances distinct modes of actin assembly for growth versus retraction. Author summary Neurons may extend highly branched dendrites to detect input over a broad receptive field. The formation of actin filaments may drive dendrite elongation. The architecture of the dendritic arbor also depends on mechanisms that limit expansion. For example, sister dendrites from a single neuron usually do not overlap due to self-avoidance. Although cell surface proteins are known to mediate self-avoidance, the downstream pathways that drive dendrite retraction in this phenomenon are largely unknown. Studies of the highly branched PVD sensory neuron in C. elegans have suggested a model of self-avoidance in which the UNC-40/DCC receptor captures the diffusible cue UNC-6/Netrin at the tips of PVD dendrites where it interacts with the UNC-5 receptor on an opposing sister dendrite to induce retraction. Here we report genetic evidence that UNC-5-dependent retraction requires downstream actin polymerization. This finding evokes a paradox: How might actin polymerization drive both dendrite growth and retraction? We propose two answers: (1) Distinct sets of effectors are involved in actin assembly for growth vs retraction; (2) Non-muscle myosin interacts with a nascent actin assemblage to trigger retraction. Our results show that dendrite length depends on the balanced effects of specific molecular components that induce growth vs retraction.en_US
dc.description.sponsorshipThis work was supported by NIH Grants R01 NS079611 to DMM, F31 NS071801 to CJS and F31 NS49743 to JDW. Some of the strains used in this work were provided by the C. elegans Genetics Center, which is supported by the US National Institutes of Health (NIH) National Center for Research Resources. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.en_US
dc.publisherPLOS GENETICSen_US
dc.rightsCopyright: © 2019 Sundararajan et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
dc.subjectARP2/3 COMPLEXen_US
dc.subjectAXON GUIDANCEen_US
dc.subjectC. ELEGANSen_US
dc.subjectRECEPTOR UNC-40/DCCen_US
dc.titleActin assembly and non-muscle myosin activity drive dendrite retraction in an UNC-6/Netrin dependent self-avoidance responseen_US

Files in this item


This item appears in the following Collection(s)

Show simple item record