Distinct Cell Guidance Pathways Controlled by the Rac and Rho GEF Domains of UNC-73/TRIO in <i>Caenorhabditis elegans</i>

Marcus-Gueret, Nancy; Schmidt, Kristopher L.; Stringham, Eve G.

doi:10.1534/genetics.111.134429

Cited by 20 publications

(22 citation statements)

References 56 publications

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“…pVA700 is a derivative of the Fire vector pPD95.77 which contains the pgp-12 promoter (Marcus-Gueret et al, 2012). Plasmids (160 ng/ul) were injected into worms using standard techniques, using coinjection marker Punc-122∷dsRed (40ng/μl).…”

Section: Methodsmentioning

confidence: 99%

Abelson interactor-1 (ABI-1) interacts with MRL adaptor protein MIG-10 and is required in guided cell migrations and process outgrowth in C. elegans

McShea

Schmidt

Dubuke

et al. 2013

Developmental Biology

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Directed cell migration and process outgrowth are vital to proper development of many metazoan tissues. These processes are dependent on reorganization of the actin cytoskeleton in response to external guidance cues. During development of the nervous system, the MIG-10/RIAM/Lamellipodin (MRL) signaling proteins are thought to transmit positional information from surface guidance cues to the actin polymerization machinery, and thus to promote polarized outgrowth of axons. In C. elegans, mutations in the MRL family member gene mig-10 result in animals that have defects in axon guidance, neuronal migration, and the outgrowth of the processes or ‘canals’ of the excretory cell, which is required for osmoregulation in the worm. In addition, mig-10 mutant animals have recently been shown to have defects in clustering of vesicles at the synapse. To determine additional molecular partners of MIG-10, we conducted a yeast two hybrid screen using isoform MIG-10A as bait and isolated Abelson-interactor protein-1 (ABI-1). ABI-1, a downstream target of Abl non-receptor tyrosine kinase, is a member of the WAVE regulatory complex (WRC) involved in the initiation of actin polymerization. Further analysis using a co-mmunoprecipitation system confirmed the interaction of MIG-10 and ABI-1 and showed that it requires the SH3 domain of ABI-1. Single mutants for mig-10 and abi-1 displayed similar phenotypes of incomplete migration of the ALM neurons and truncated outgrowth of the excretory cell canals, suggesting that the ABI-1/MIG-10 interaction is relevant in vivo. Cell autonomous expression of MIG-10 isoforms rescued both the neuronal migration and the canal outgrowth defects, showing that MIG-10 functions autonomously in the ALM neurons and the excretory cell. These results suggest that MIG-10 and ABI-1 interact physically to promote cell migration and process outgrowth in vivo. In the excretory canal, ABI-1 is thought to act downstream of UNC-53/NAV2, linking this large scaffolding protein to actin polymerization during excretory canal outgrowth. abi-1(RNAi) enhanced the excretory canal truncation observed in mig-10 mutants, while double mutant analysis between unc-53 and mig-10 showed no increased truncation of the posterior canal beyond that observed in mig-10 mutants. Morphological analysis of mig-10 and unc-53 mutants showed that these genes regulate canal diameter as well as its length, suggesting that defective lumen formation may be linked to the ability of the excretory canal to grow out longitudinally. Taken together, our results suggest that MIG-10, UNC-53, and ABI-1 act sequentially to mediate excretory cell process outgrowth.

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Section: Methodsmentioning

confidence: 99%

Abelson interactor-1 (ABI-1) interacts with MRL adaptor protein MIG-10 and is required in guided cell migrations and process outgrowth in C. elegans

McShea

Schmidt

Dubuke

et al. 2013

Developmental Biology

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“…The activity of the GEF domains of these proteins maybe controlled by SH3 auto inhibition and they have been implicated in synaptic structure and function (Marcus-Gueret et al, 2012). However, there is no evidence that this is controlled by mutual interaction with nlg-1.…”

Section: Discussionmentioning

confidence: 99%

Analysis of splice variants for the C. elegans orthologue of human neuroligin reveals a developmentally regulated transcript

Calahorro

Holden‐Dye

O’Connor

2015

Gene Expression Patterns

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“…UNC-53, homologous to vertebrate NAV2, is an actin-and MT-binding protein that affects many anterior-posterior cell and axon migrations, as well as canal outgrowth (Stringham et al 2002). UNC-53 acts cell autonomously and in a common pathway with UNC-71 (ADAM), MIG-10 (Lamellipodin), ABI-1 (Abelson Interactor-1), WVE-1 (WAVE), ARX-2 (Arp2), and the Rho-specific guanine nucleotide exchange activity of UNC-73 (TRIO) (Schmidt et al 2009;Marcus-Gueret et al 2012; McShea (2015) and Khan et al (2013) (not to scale). EXC-6/INF2 formin is spread throughout the canal and concentrated at varicosities and especially at the canal tip, where it helps to form a large actin patch to push the membrane forward.…”

Section: Cytoskeletal Organization In the Growing Canalsmentioning

confidence: 99%

The Caenorhabditis elegans Excretory System: A Model for Tubulogenesis, Cell Fate Specification, and Plasticity

Sundaram

Buechner

2016

Genetics

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The excretory system of the nematode Caenorhabditis elegans is a superb model of tubular organogenesis involving a minimum of cells. The system consists of just three unicellular tubes (canal, duct, and pore), a secretory gland, and two associated neurons. Just as in more complex organs, cells of the excretory system must first adopt specific identities and then coordinate diverse processes to form tubes of appropriate topology, shape, connectivity, and physiological function. The unicellular topology of excretory tubes, their varied and sometimes complex shapes, and the dynamic reprogramming of cell identity and remodeling of tube connectivity that occur during larval development are particularly fascinating features of this organ. The physiological roles of the excretory system in osmoregulation and other aspects of the animal's life cycle are only beginning to be explored. The cellular mechanisms and molecular pathways used to build and shape excretory tubes appear similar to those used in both unicellular and multicellular tubes in more complex organs, such as the vertebrate vascular system and kidney, making this simple organ system a useful model for understanding disease processes.KEYWORDS Caenorhabditis elegans; tubulogenesis; excretory-secretory system; WormBook

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Distinct Cell Guidance Pathways Controlled by the Rac and Rho GEF Domains of UNC-73/TRIO in Caenorhabditis elegans

Cited by 20 publications

References 56 publications

Abelson interactor-1 (ABI-1) interacts with MRL adaptor protein MIG-10 and is required in guided cell migrations and process outgrowth in C. elegans

Abelson interactor-1 (ABI-1) interacts with MRL adaptor protein MIG-10 and is required in guided cell migrations and process outgrowth in C. elegans

Analysis of splice variants for the C. elegans orthologue of human neuroligin reveals a developmentally regulated transcript

The Caenorhabditis elegans Excretory System: A Model for Tubulogenesis, Cell Fate Specification, and Plasticity

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