<i>C. elegans</i> CARMIL negatively regulates UNC-73/Trio function during neuronal development

Vanderzalm, Pamela J.; Pandey, Amita; Hurwitz, Michael; Bloom, Laird; Horvitz, H. Robert; Garriga, Gian

doi:10.1242/dev.026666

Cited by 36 publications

(33 citation statements)

References 43 publications

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“…In CARMIL1 knockdown cells, Rac1 activity was decreased, consistent with inhibition of lamellipodia. In addition, we found that CARMIL1 associates with the Rac-GEF Trio, as recently observed in C. elegans (Vanderzalm et al, 2009). Thus, CARMIL1 may control lamellipodial actin assembly via effects on Trio and Rac1.…”

Section: Discussionsupporting

confidence: 87%

“…In contrast, in CARMIL1i cells, the level of active Rac1 did not change. A recent study in C. elegans found biochemical and genetic interactions between CARMIL and Trio/UNC-73, a large protein with both Rac-and Rho-GEF domains (Vanderzalm et al, 2009). We looked for a biochemical interaction between CARMILs and Trio in our cells, by coimmunoprecipitation.…”

Section: Effects Of Carmil1 On Lamellipodial Actinmentioning

confidence: 96%

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Distinct Roles for CARMIL Isoforms in Cell Migration

Liang

Niederstrasser

Edwards

et al. 2009

MBoC

137

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Molecular mechanisms for cell migration, especially how signaling and cytoskeletal systems are integrated, are not understood well. Here, we examined the role of CARMIL (capping protein, Arp2/3, and Myosin-I linker) family proteins in migrating cells. Vertebrates express three conserved genes for CARMIL, and we examined the functions of the two CARMIL genes expressed in migrating human cultured cells. Both isoforms, CARMIL1 and 2, were necessary for cell migration, but for different reasons. CARMIL1 localized to lamellipodia and macropinosomes, and loss of its function caused loss of lamellipodial actin, along with defects in protrusion, ruffling, and macropinocytosis. CARMIL1-knockdown cells showed loss of activation of Rac1, and CARMIL1 was biochemically associated with the GEF Trio. CARMIL2, in contrast, colocalized with vimentin intermediate filaments, and loss of its function caused a distinctive multipolar phenotype. Loss of CARMIL2 also caused decreased levels of myosin-IIB, which may contribute to the polarity phenotype. Expression of one CARMIL isoform was not able to rescue the knockdown phenotypes of the other. Thus, the two isoforms are both important for cell migration, but they have distinct functions.

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Section: Discussionsupporting

confidence: 87%

Section: Effects Of Carmil1 On Lamellipodial Actinmentioning

confidence: 96%

Distinct Roles for CARMIL Isoforms in Cell Migration

Liang

Niederstrasser

Edwards

et al. 2009

MBoC

137

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“…By contrast, recent work indicates that UNC-73/Trio can also be negatively regulated by the CRML-1/CARMIL (Capping, Arp2/3, Myosin I Linker) protein. This decreases the levels of SAX-3/Robo at the membrane (Vanderzalm et al, 2009) (Fig. 4D).…”

Section: Slit/robo and Netrin 1/dcc Inter-regulationmentioning

confidence: 91%

Moving away from the midline: new developments for Slit and Robo

2010

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SummaryIn most tissues, the precise control of cell migration and cellcell interaction is of paramount importance to the development of a functional structure. Several families of secreted molecules have been implicated in regulating these aspects of development, including the Slits and their Robo receptors. These proteins have well described roles in axon guidance but by influencing cell polarity and adhesion, they participate in many developmental processes in diverse cell types. We review recent progress in understanding both the molecular mechanisms that modulate Slit/Robo expression and their functions in neural and non-neural tissue. Key words: Axon guidance, Cell migration, Cell-cell interaction IntroductionIn most organisms, the central nervous system (CNS) develops along a bilateral axis of symmetry located at the midline (Placzek and Briscoe, 2005). During development, the ventral midline or floor plate acts as an organiser through the secretion of diffusible proteins (Placzek and Briscoe, 2005;Gore et al., 2008), which control the growth of axons and dendrites and the migration of neurons across the midline. In the forebrain, glial or neuronal cells delineate the midline (see Glossary, Box 1) and also control axon guidance. For more than two decades, many developmental neurobiologists have tried to understand the mechanisms that control midline crossing in the CNS and to answer some key questions. Firstly, how are commissural axons (see Glossary, Box 1) attracted to the midline and how do their growth cones (see Glossary, Box1) receive and integrate the multiple and contrasting signals released by midline cells? Secondly, what are the molecular and signalling changes that enable commissural axons to leave the midline and often to switch to a longitudinal growth mode? All midline-derived axon guidance factors are expressed at other locations in many developing and mature tissues, where they control a wide range of biological processes.Roundabout receptors (Robo) and their Slit ligands form one of the most crucial ligand-receptor pairings among the axon guidance molecules. Robos were identified in Drosophila in a mutant screen for genes that control the midline crossing of commissural axons (Kidd et al., 1998;Seeger et al., 1993). Similarly, Slit was discovered in Drosophila as a protein secreted by midline glia (Rothberg et al., 1988;Rothberg et al., 1990). Homologues of both proteins have since been discovered in many species (for a review, see . However, the Slit/Robo couple not only functions in axon guidance but also in a variety of developmental Development 137, 1939Development 137, -1952Development 137, (2010 Commissural axons Axons with cell bodies (somata) located on one side of the central nervous system (CNS) that project axons across the midline to contact target cells on the opposite side. Growth cone A specialised bulbous enlargement at the end of growing axons that is characterised by dynamic filamentous extensions, known as filopodia. They sense the environment and respond to adhesi...

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“…Initially puzzled by this, we soon discovered Gian Garriga's group had identified a novel, conserved protein that can form a complex with UNC-73, capping Arp2/3 myosin I linker, CRML-1/CARMIL. 25,26 In growth cones, crml-1 loss can suppress unc-73 mutants, placing CRML-1 and UNC-73 in both a physical and functional pathway. In the dorsal epidermis crml-1 loss resulted in excessive protrusions, particularly at non-medial edges, where protrusions are normally absent.…”

Section: 24mentioning

confidence: 99%

Another morphogenetic movement on the map: Charting dorsal intercalation inC. elegans

Walck-Shannon

Hardin

2016

Worm

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Dorsal intercalation is a coordinated cell migration event that rearranges hypodermal cells during C. elegans embryogenesis, and that resembles cell intercalation in many systems from flies to mice. Despite its conservation, the molecular mechanisms that govern dorsal intercalation in worms have remained elusive. Here, we comment on our recent publication, Walck-Shannon et al.,1 which begins to spatially map the molecular requirements for intercalation. First, we provide a historical perspective on the factors that have previously hampered the study of dorsal intercalation. Next, we provide a summary of the molecular pathways identified in Walck-Shannon et al.,1 pointing out surprises along the way. Finally, we consider the potential conservation of the molecular pathway we described and discuss future questions surrounding dorsal intercalation. Despite the challenges, dorsal intercalation is a process poised to advance our understanding of cell intercalation during morphogenesis throughout the animal kingdom.

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C. elegans CARMIL negatively regulates UNC-73/Trio function during neuronal development

Cited by 36 publications

References 43 publications

Distinct Roles for CARMIL Isoforms in Cell Migration

Distinct Roles for CARMIL Isoforms in Cell Migration

Moving away from the midline: new developments for Slit and Robo

Another morphogenetic movement on the map: Charting dorsal intercalation inC. elegans

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