Many unicellular tubes such as capillaries form lumens intracellularly, a process that is not well understood. Here we show that the cortical membrane organizer ERM-1 is required to expand the intracellular apical/lumenal membrane and its actin undercoat during single-cell Caenorhabditis elegans excretory canal morphogenesis. We characterize AQP-8, identified in an ERM-1-overexpression (ERM-1[++]) suppressor screen, as a canalicular aquaporin that interacts with ERM-1 in lumen extension in a mercury-sensitive manner, implicating water-channel activity. AQP-8 is transiently recruited to the lumen by ERM-1, co-localizing in peri-lumenal cuffs interspaced along expanding canals. An ERM-1[++]-mediated increase in the number of lumen-associated canaliculi is reversed by AQP-8 depletion. We propose that the ERM-1/AQP-8 interaction propels lumen extension by translumenal flux, suggesting a direct morphogenetic effect of water-channel-regulated fluid pressure.
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We thank D. Baillie (Simon Fraser University, Burnaby, British Columbia, Canada), M. Futai (Osaka University, Osaka, Japan), M. Labouesse (IGBMC, France), K. Nehrke (University of Rochester Medical Center, Rochester New York, USA) and J. Simske (Case Western Reserve University School of Medicine, Cleveland, Ohio, USA), and the following C. elegans resource centres: J. Kohara (National Institute of Genetics, Mishima, Japan), S. Mitani (National Bioresource Project, Tokyo Women’s Medical University, Tokyo, Japan), the International C. elegans Gene Knockout Consortium and the Caenorhabditis elegans genetic centre (NIH Center for Research Resources) for providing plasmids and strains. We thank E. Membreno and D. Fernandez for technical support, A. Sengupta for three-dimensional graphics, A. Kim for image editing, F. Solomon for critical reading of the manuscript, and H. Weinstein and A. Walker for ongoing support. This work was supported by NIH grant GM078653 and a Mattina R. Proctor Award to V.G.
The authors declare no competing financial interests.
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Khan, L., Zhang, H., Abraham, N. et al. Intracellular lumen extension requires ERM-1-dependent apical membrane expansion and AQP-8-mediated flux. Nat Cell Biol 15, 143–156 (2013). https://doi.org/10.1038/ncb2656
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