The secretory pathway, linked to recycling routes, specifies epithelial membrane polarity

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	The secretory pathway, linked to recycling routes, specifies epithelial membrane polarity
	Zhang, N; Zhang, H.; Khan, L.; Jafai, G.; Eun, Y.; Membreno, E.; Gobel, V.
	2019-06-01
Source Publication	22nd International C. elegans Conference Abstract Book
Abstract	Current polarity models propose that membrane-/junction-based polarity determinants position apicobasal membrane domains of epithelial cells, while intracellular vesicular trafficking only maintains, but does not position, these domains. Previously, we and others showed that interference with trafficking converts polarity on expanding membranes of embryonic or larval C. elegans intestines. Depleting vesicle-membrane- and coat components (glycosphingolipids/GSLs and clathrin/AP-1) misplaces apical domains and lumens to basolateral sides, suggesting that trafficking positions the apical domain. To assess the role of trafficking in polarity conversion, we used a two-tiered genomic/genetic screen approach. From several large-scale tubulogenesis screens, we collected all trafficking molecules found to affect apical membrane and lumen biogenesis in the multicellular intestine and unicellular excretory canal. 50 identified molecules were then tested in genetic interaction screens for their ability to modify the GSL-dependent intestinal polarity conversion. Strikingly, GSL enhancers were strongly enriched for components of the biosynthetic/secretory trafficking pathway. Moreover, these enhancers and multiple additional secretory molecules (including SEC-23/SEC-24), were subsequently characterized as independent apical polarity cues in wild-type. Interference with each disrupted membrane-directed trafficking (expected), but, unexpectedly, also displaced apical membrane components to basolateral domains. In contrast, GSL suppressors uncovered several endocytic recycling components supplementing the biosynthetic route, identifying new roles for RAB-7, DAB-1/Disabled, and the V-ATPase VHA-6 in polarized recycling. Our findings suggest a different mechanism of membrane polarization, where the secretory pathway, linked to recycling routes, becomes apically determinate during polarized membrane expansion and preferentially supplies the apical domain, thereby specifying membrane polarity.
Keyword	Secretory pathway recycling routes epithelial membrane polarity
Language	英語English
The Source to Article	PB_Publication
PUB ID	46798
Document Type	Conference paper
Collection	DEPARTMENT OF BIOMEDICAL SCIENCES Faculty of Health Sciences
Corresponding Author	Gobel, V.
Recommended Citation GB/T 7714	Zhang, N,Zhang, H.,Khan, L.,et al. The secretory pathway, linked to recycling routes, specifies epithelial membrane polarity[C], 2019.
APA	Zhang, N., Zhang, H.., Khan, L.., Jafai, G.., Eun, Y.., Membreno, E.., & Gobel, V. (2019). The secretory pathway, linked to recycling routes, specifies epithelial membrane polarity. 22nd International C. elegans Conference Abstract Book.

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