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 C. 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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All data generated or analyzed during this study are included in the manuscript and supporting files. Source data files have been provided for Figures 2, 3, 5, 6, and 7.

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Joshua Abrams

Skirball Institute of Biomolecular Medicine, NYU Grossman School of Medicine, New York, United States

Competing interests
The authors declare that no competing interests exist.
Jeremy Nance

Skirball Institute of Biomolecular Medicine, NYU Grossman School of Medicine, New York, United States

For correspondence
jeremy.nance@med.nyu.edu

Competing interests
The authors declare that no competing interests exist.

"This ORCID iD identifies the author of this article:" 0000-0003-4212-7731

Funding

American Cancer Society (PF-16-175-01-DDC)

Joshua Abrams

National Institutes of Health (F32HL136038)

Joshua Abrams

National Institutes of Health (R01GM098492)

Jeremy Nance

National Institutes of Health (R35GM118081)

Jeremy Nance

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

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