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

Sundararajan, Lakshmi; Smith, Cody J.; Watson, Joseph D.; Millis, Bryan A.; Tyska, Matthew J.; Miller, David M.

doi:10.1371/journal.pgen.1008228

Cited by 28 publications

(33 citation statements)

References 73 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…5A). We found that, consistent with the importance of Ena/VASP proteins in elongating actin bundles, and with a recent report describing UNC-34 localization in PVD [24], UNC-34:GFP was enriched as puncta at the tips of growing dendrites (Fig. 5B, F; Additional file 6).…”

Section: The Evh1 Domain Of Unc-34 Is Necessary For Unc-34 Localization and Function In Vivosupporting

confidence: 92%

“…A multipartite ligand-receptor complex, consisting of the extracellular ligands SAX-7, MNR-1, and LECT-2, along with the PVD guidance receptor DMA-1 and its partner HPO-30, directs the growth of PVD dendrites along the epidermis and body wall muscles [19][20][21][22][23]. This ligand-receptor complex recruits actin regulators, including the Rac GEF TIAM-1 and the WRC, through the cytosolic domains of DMA-1 and HPO-30, respectively, which in turn produce F-actin in growing dendrite tips to drive dendrite branching [23][24][25]. However, the mechanisms of F-actin recruitment during distinct morphological steps during dendrite development, such as initiation of new branches and branch elongation, remain unclear.…”

mentioning

confidence: 99%

See 1 more Smart Citation

A two-step actin polymerization mechanism drives dendrite branching

et al. 2021

View full text Add to dashboard Cite

Background Dendrite morphogenesis plays an essential role in establishing the connectivity and receptive fields of neurons during the development of the nervous system. To generate the diverse morphologies of branched dendrites, neurons use external cues and cell surface receptors to coordinate intracellular cytoskeletal organization; however, the molecular mechanisms of how this signaling forms branched dendrites are not fully understood. Methods We performed in vivo time-lapse imaging of the PVD neuron in C. elegans in several mutants of actin regulatory proteins, such as the WAVE Regulatory Complex (WRC) and UNC-34 (homolog of Enabled/Vasodilator-stimulated phosphoprotein (Ena/VASP)). We examined the direct interaction between the WRC and UNC-34 and analyzed the localization of UNC-34 in vivo using transgenic worms expressing UNC-34 fused to GFP. Results We identify a stereotyped sequence of morphological events during dendrite outgrowth in the PVD neuron in C. elegans. Specifically, local increases in width (“swellings”) give rise to filopodia to facilitate a “rapid growth and pause” mode of growth. In unc-34 mutants, filopodia fail to form but swellings are intact. In WRC mutants, dendrite growth is largely absent, resulting from a lack of both swelling and filopodia formation. We also found that UNC-34 can directly bind to the WRC. Disrupting this binding by deleting the UNC-34 EVH1 domain prevented UNC-34 from localizing to swellings and dendrite tips, resulting in a stunted dendritic arbor and reduced filopodia outgrowth. Conclusions We propose that regulators of branched and linear F-actin cooperate to establish dendritic branches. By combining our work with existing literature, we propose that the dendrite guidance receptor DMA-1 recruits the WRC, which polymerizes branched F-actin to generate “swellings” on a mother dendrite. Then, WRC recruits the actin elongation factor UNC-34/Ena/VASP to initiate growth of a new dendritic branch from the swelling, with the help of the actin-binding protein UNC-115/abLIM. Extension of existing dendrites also proceeds via swelling formation at the dendrite tip followed by UNC-34-mediated outgrowth. Following dendrite initiation and extension, the stabilization of branches by guidance receptors further recruits WRC, resulting in an iterative process to build a complex dendritic arbor.

show abstract

Section: The Evh1 Domain Of Unc-34 Is Necessary For Unc-34 Localization and Function In Vivosupporting

confidence: 92%

mentioning

confidence: 99%

A two-step actin polymerization mechanism drives dendrite branching

et al. 2021

View full text Add to dashboard Cite

show abstract

“…While the local cytoskeletal composition of mature arbors was surprisingly predictive of overall dendritic size and complexity, this study did not model the geometric shape of the arbors, which results from a combination of several factors including stem orientation ( Samsonovich and Ascoli, 2003 ) and branch angles ( Bielza et al., 2014 ), self-avoidance ( Kidd and Condron, 2007 ; Sundararajan et al., 2019 ), and tiling ( Grueber et al., 2002 ). Dendritic pruning ( Herzmann et al., 2018 ) and underlying developmental processes such as the polymerization, depolymerization, bundling, severing of MTs or F-act, traffics of cargos, and stoichiometry of MTs and F-act are also not accounted for in the model.…”

Section: Discussionmentioning

confidence: 92%

Distinct Relations of Microtubules and Actin Filaments with Dendritic Architecture

et al. 2020

View full text Add to dashboard Cite

“…Briefly, the two putative cell adhesion molecules SAX-7/L1CAM and MNR-1/Menorin form a complex in the epidermis, which, together with the muscle derived chemokine LECT-2/Chondromodulin II forms a high affinity substrate for the leucine rich repeat transmembrane receptor DMA-1/LRR-TM, which functions in PVD neurons. Downstream of DMA-1/LRR-TM in PVD function is a conserved set of intracellular molecules such as the TIAM-1/GEF guanine nucleotide exchange factor and HPO-30/Claudin, which together regulate the actin cytoskeleton [8,35]. Previous genetic experiments established that SAX-7/L1CAM, LECT-2/Chondromodulin II and MNR-1/Menorin function in a linear genetic pathway with the DMA-1/LRR-TM receptor, but also suggested that DMA-1 can serve functions in PVD patterning that are independent of SAX-7/L1CAM, MNR-1/Menorin and LECT-2/Chondromodulin.…”

Section: Catp-8/p5a Atpase Functions In the Menorin Pathway To Pattermentioning

confidence: 99%

The CATP-8/P5A-type ATPase functions in multiple pathways during neuronal patterning

Tang

Trivedi

Freund

et al. 2021

Preprint

View full text Add to dashboard Cite

The assembly of neuronal circuits involves the migrations of neurons from their place of birth to their final location in the nervous system, as well as the coordinated growth and patterning of axons and dendrites. In screens for genes required for patterning of the nervous system, we identified the catp-8/P5A-ATPase as an important regulator of neural patterning. P5A-ATPases are part of the P-type ATPases, a family of proteins known to serve a conserved function as transporters of ions, lipids and polyamines in unicellular eukaryotes, plants, and humans. While the function of many P-type ATPases is relatively well understood, the function of P5A-ATPases in metazoans remained elusive. We show here, that the Caenorhabditis elegans ortholog catp-8/P5A-ATPase is required for specific aspects of nervous system development. Specifically, the catp-8/P5A-ATPase serves functions in shaping the elaborately sculpted dendritic trees of somatosensory PVD neurons. Moreover, catp-8/P5A-ATPase is required for axonal guidance and repulsion at the midline, as well as embryonic and postembryonic neuronal migrations. Interestingly, not all axons at the midline require catp-8/P5A-ATPase , although the axons run in the same fascicles and navigate the same space. Similarly, not all neuronal migrations require catp-8/P5A-ATPase . A CATP -8/P5A-ATPase reporter is localized to the ER in most if not all tissues and catp-8/P5A-ATPase can function both cell-autonomously and non-autonomously to regulate neuronal development. Genetic analyses establish that catp-8/P5A-ATPase can function in multiple pathways, including the Menorin pathway, previously shown to control dendritic patterning in PVD, and Wnt signaling, which functions to control neuronal migrations. Lastly, we show that catp-8/P5A-ATPase is required for localizing select transmembrane proteins necessary for dendrite morphogenesis. Collectively, our studies suggest that catp-8/P5A-ATPase serves diverse, yet specific roles in different genetic pathways, and may be involved in the regulation or localization of transmembrane proteins to specific subcellular compartments.

show abstract

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

Cited by 28 publications

References 73 publications

A two-step actin polymerization mechanism drives dendrite branching

A two-step actin polymerization mechanism drives dendrite branching

Distinct Relations of Microtubules and Actin Filaments with Dendritic Architecture

The CATP-8/P5A-type ATPase functions in multiple pathways during neuronal patterning

Contact Info

Product

Resources

About