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Opposing Activities of LIT-1/NLK and DAF-6/Patched-Related Direct Sensory Compartment Morphogenesis in C. elegans

Glial cells surround neuronal endings to create enclosed compartments required for neuronal function. This architecture is seen at excitatory synapses and at sensory neuron receptive endings. Despite the prevalence and importance of these compartments, how they form is not known. We used the main se...

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Autores principales: Oikonomou, Grigorios, Perens, Elliot A., Lu, Yun, Watanabe, Shigeki, Jorgensen, Erik M., Shaham, Shai
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2011
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3153439/
https://www.ncbi.nlm.nih.gov/pubmed/21857800
http://dx.doi.org/10.1371/journal.pbio.1001121
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author Oikonomou, Grigorios
Perens, Elliot A.
Lu, Yun
Watanabe, Shigeki
Jorgensen, Erik M.
Shaham, Shai
author_facet Oikonomou, Grigorios
Perens, Elliot A.
Lu, Yun
Watanabe, Shigeki
Jorgensen, Erik M.
Shaham, Shai
author_sort Oikonomou, Grigorios
collection PubMed
description Glial cells surround neuronal endings to create enclosed compartments required for neuronal function. This architecture is seen at excitatory synapses and at sensory neuron receptive endings. Despite the prevalence and importance of these compartments, how they form is not known. We used the main sensory organ of C. elegans, the amphid, to investigate this issue. daf-6/Patched-related is a glia-expressed gene previously implicated in amphid sensory compartment morphogenesis. By comparing time series of electron-microscopy (EM) reconstructions of wild-type and daf-6 mutant embryos, we show that daf-6 acts to restrict compartment size. From a genetic screen, we found that mutations in the gene lit-1/Nemo-like kinase (NLK) suppress daf-6. EM and genetic studies demonstrate that lit-1 acts within glia, in counterbalance to daf-6, to promote sensory compartment expansion. Although LIT-1 has been shown to regulate Wnt signaling, our genetic studies demonstrate a novel, Wnt-independent role for LIT-1 in sensory compartment size control. The LIT-1 activator MOM-4/TAK1 is also important for compartment morphogenesis and both proteins line the glial sensory compartment. LIT-1 compartment localization is important for its function and requires neuronal signals. Furthermore, the conserved LIT-1 C-terminus is necessary and sufficient for this localization. Two-hybrid and co-immunoprecipitation studies demonstrate that the LIT-1 C-terminus binds both actin and the Wiskott-Aldrich syndrome protein (WASP), an actin regulator. We use fluorescence light microscopy and fluorescence EM methodology to show that actin is highly enriched around the amphid sensory compartment. Finally, our genetic studies demonstrate that WASP is important for compartment expansion and functions in the same pathway as LIT-1. The studies presented here uncover a novel, Wnt-independent role for the conserved Nemo-like kinase LIT-1 in controlling cell morphogenesis in conjunction with the actin cytoskeleton. Our results suggest that the opposing daf-6 and lit-1 glial pathways act together to control sensory compartment size.
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spelling pubmed-31534392011-08-19 Opposing Activities of LIT-1/NLK and DAF-6/Patched-Related Direct Sensory Compartment Morphogenesis in C. elegans Oikonomou, Grigorios Perens, Elliot A. Lu, Yun Watanabe, Shigeki Jorgensen, Erik M. Shaham, Shai PLoS Biol Research Article Glial cells surround neuronal endings to create enclosed compartments required for neuronal function. This architecture is seen at excitatory synapses and at sensory neuron receptive endings. Despite the prevalence and importance of these compartments, how they form is not known. We used the main sensory organ of C. elegans, the amphid, to investigate this issue. daf-6/Patched-related is a glia-expressed gene previously implicated in amphid sensory compartment morphogenesis. By comparing time series of electron-microscopy (EM) reconstructions of wild-type and daf-6 mutant embryos, we show that daf-6 acts to restrict compartment size. From a genetic screen, we found that mutations in the gene lit-1/Nemo-like kinase (NLK) suppress daf-6. EM and genetic studies demonstrate that lit-1 acts within glia, in counterbalance to daf-6, to promote sensory compartment expansion. Although LIT-1 has been shown to regulate Wnt signaling, our genetic studies demonstrate a novel, Wnt-independent role for LIT-1 in sensory compartment size control. The LIT-1 activator MOM-4/TAK1 is also important for compartment morphogenesis and both proteins line the glial sensory compartment. LIT-1 compartment localization is important for its function and requires neuronal signals. Furthermore, the conserved LIT-1 C-terminus is necessary and sufficient for this localization. Two-hybrid and co-immunoprecipitation studies demonstrate that the LIT-1 C-terminus binds both actin and the Wiskott-Aldrich syndrome protein (WASP), an actin regulator. We use fluorescence light microscopy and fluorescence EM methodology to show that actin is highly enriched around the amphid sensory compartment. Finally, our genetic studies demonstrate that WASP is important for compartment expansion and functions in the same pathway as LIT-1. The studies presented here uncover a novel, Wnt-independent role for the conserved Nemo-like kinase LIT-1 in controlling cell morphogenesis in conjunction with the actin cytoskeleton. Our results suggest that the opposing daf-6 and lit-1 glial pathways act together to control sensory compartment size. Public Library of Science 2011-08-09 /pmc/articles/PMC3153439/ /pubmed/21857800 http://dx.doi.org/10.1371/journal.pbio.1001121 Text en Oikonomou et al. http://creativecommons.org/licenses/by/4.0/ 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 properly credited.
spellingShingle Research Article
Oikonomou, Grigorios
Perens, Elliot A.
Lu, Yun
Watanabe, Shigeki
Jorgensen, Erik M.
Shaham, Shai
Opposing Activities of LIT-1/NLK and DAF-6/Patched-Related Direct Sensory Compartment Morphogenesis in C. elegans
title Opposing Activities of LIT-1/NLK and DAF-6/Patched-Related Direct Sensory Compartment Morphogenesis in C. elegans
title_full Opposing Activities of LIT-1/NLK and DAF-6/Patched-Related Direct Sensory Compartment Morphogenesis in C. elegans
title_fullStr Opposing Activities of LIT-1/NLK and DAF-6/Patched-Related Direct Sensory Compartment Morphogenesis in C. elegans
title_full_unstemmed Opposing Activities of LIT-1/NLK and DAF-6/Patched-Related Direct Sensory Compartment Morphogenesis in C. elegans
title_short Opposing Activities of LIT-1/NLK and DAF-6/Patched-Related Direct Sensory Compartment Morphogenesis in C. elegans
title_sort opposing activities of lit-1/nlk and daf-6/patched-related direct sensory compartment morphogenesis in c. elegans
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3153439/
https://www.ncbi.nlm.nih.gov/pubmed/21857800
http://dx.doi.org/10.1371/journal.pbio.1001121
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