A V0-ATPase-dependent apical trafficking pathway maintains the polarity of the intestinal absorptive membrane

• Published in: Development (Cambridge) Vol. 146; no. 11
• Main Authors: Bidaud-Meynard, Aurélien, Nicolle, Ophélie, Heck, Markus, Le Cunff, Yann, Michaux, Grégoire
• Format: Journal Article
• Language: English
• Published: England Company of Biologists 05.06.2019; The Company of Biologists Ltd
• Subjects: Animals; Animals, Genetically Modified; Caenorhabditis elegans; Caenorhabditis elegans Proteins - physiology; Cell Membrane - metabolism; Cell Membrane - physiology; Cell Polarity - genetics; Cellular Biology; Enterocytes - physiology; Intestinal Absorption - genetics; Intestinal Mucosa - metabolism; Intestinal Mucosa - physiology; Life Sciences; Protein Transport - genetics; Proton-Translocating ATPases - physiology; Signal Transduction; Vacuolar Proton-Translocating ATPases - physiology; Polarity; C. elegans; Epithelial cells; Intestine; Microvillus inclusion disease; Trafficking
• ISSN: 0950-1991; 1477-9129; 1477-9129
• DOI: 10.1242/dev.174508

Intestine function relies on the strong polarity of intestinal epithelial cells and the array of microvilli forming a brush border at their luminal pole. Combining a genetic RNA interference (RNAi) screen with super-resolution imaging in the intestine, we found that the V0 sector of the vacuolar ATPase (V0-ATPase) controls a late apical trafficking step, involving Ras-related protein 11 (RAB-11) endosomes and the -ethylmaleimide-sensitive factor-attachment protein receptor (SNARE) synaptosome-associated protein 29 (SNAP-29), and is necessary to maintain the polarized localization of both apical polarity modules and brush border proteins. We show that the V0-ATPase pathway also genetically interacts with glycosphingolipids and clathrin in enterocyte polarity maintenance. Finally, we demonstrate that silencing of the V0-ATPase fully recapitulates the severe structural, polarity and trafficking defects observed in enterocytes from individuals with microvillus inclusion disease (MVID) and use this new MVID model to follow the dynamics of microvillus inclusions. Thus, we describe a new function for V0-ATPase in apical trafficking and epithelial polarity maintenance and the promising use of the intestine as an model to better understand the molecular mechanisms of rare genetic enteropathies.