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      A polarity pathway for exocyst-dependent intracellular tube extension

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          Abstract

          Lumen extension in intracellular tubes can occur when vesicles fuse with an invading apical membrane. Within the Caenorhabditis elegans excretory cell, which forms an intracellular tube, the exocyst vesicle-tethering complex is enriched at the lumenal membrane and is required for its outgrowth, suggesting that exocyst-targeted vesicles extend the lumen. Here, we identify a pathway that promotes intracellular tube extension by enriching the exocyst at the lumenal membrane. We show that PAR-6 and PKC-3/aPKC concentrate at the lumenal membrane and promote lumen extension. Using acute protein depletion, we find that PAR-6 is required for exocyst membrane recruitment, whereas PAR-3, which can recruit the exocyst in mammals, appears dispensable for exocyst localization and lumen extension. Finally, we show that CDC-42 and RhoGEF EXC-5/FGD regulate lumen extension by recruiting PAR-6 and PKC-3 to the lumenal membrane. Our findings reveal a pathway that connects CDC-42, PAR proteins, and the exocyst to extend intracellular tubes.

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            Methods are described for the isolation, complementation and mapping of mutants of Caenorhabditis elegans, a small free-living nematode worm. About 300 EMS-induced mutants affecting behavior and morphology have been characterized and about one hundred genes have been defined. Mutations in 77 of these alter the movement of the animal. Estimates of the induced mutation frequency of both the visible mutants and X chromosome lethals suggests that, just as in Drosophila, the genetic units in C.elegans are large.
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                Author and article information

                Contributors
                Role: Reviewing Editor
                Role: Senior Editor
                Journal
                eLife
                Elife
                eLife
                eLife
                eLife Sciences Publications, Ltd
                2050-084X
                09 March 2021
                2021
                : 10
                : e65169
                Affiliations
                [1 ]deptSkirball Institute of Biomolecular Medicine NYU Grossman School of Medicine New YorkUnited States
                [2 ]Department of Cell Biology, NYU Grossman School of Medicine New YorkUnited States
                Howard Hughes Medical Institute, Stanford University United States
                Brandeis University United States
                Howard Hughes Medical Institute, Stanford University United States
                Author information
                https://orcid.org/0000-0003-1834-6782
                https://orcid.org/0000-0003-4212-7731
                Article
                65169
                10.7554/eLife.65169
                8021397
                33687331
                fde2ef9e-3566-4396-98f5-b2ef16bc4658
                © 2021, Abrams and Nance

                This article is distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use and redistribution provided that the original author and source are credited.

                History
                : 01 December 2020
                : 08 March 2021
                Funding
                Funded by: FundRef http://dx.doi.org/10.13039/100000048, American Cancer Society;
                Award ID: PF-16-175-01-DDC
                Award Recipient :
                Funded by: FundRef http://dx.doi.org/10.13039/100000002, National Institutes of Health;
                Award ID: F32HL136038
                Award Recipient :
                Funded by: FundRef http://dx.doi.org/10.13039/100000002, National Institutes of Health;
                Award ID: R01GM098492
                Award Recipient :
                Funded by: FundRef http://dx.doi.org/10.13039/100000002, National Institutes of Health;
                Award ID: R35GM118081
                Award Recipient :
                The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
                Categories
                Research Article
                Cell Biology
                Developmental Biology
                Custom metadata
                Lumen extension in intracellular tubes relies on a molecular pathway involving Rho GTPase signaling, cell polarity, and vesicle-tethering proteins.

                Life sciences
                polarity,exocyst,tubulogenesis,vesicle trafficking,par proteins,rho gtpase,c. elegans
                Life sciences
                polarity, exocyst, tubulogenesis, vesicle trafficking, par proteins, rho gtpase, c. elegans

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