title: Retromer controls epithelial cell polarity by trafficking the apical determinant Crumbs.
abstract: The evolutionarily conserved apical determinant Crumbs (Crb) is essential for maintaining apicobasal polarity and integrity of many epithelial tissues [1]. Crb levels are crucial for cell polarity and homeostasis, yet strikingly little is known about its trafficking or the mechanism of its apical localization. Using a newly established, liposome-based system described here, we determined Crb to be an interaction partner and cargo of the retromer complex. Retromer is essential for the retrograde transport of numerous transmembrane proteins from endosomes to the trans-Golgi network (TGN) and is conserved between plants, fungi, and animals [2]. We show that loss of retromer function results in a substantial reduction of Crb in Drosophila larvae, wing discs, and the follicle epithelium. Moreover, loss of retromer phenocopies loss of crb by preventing apical localization of key polarity molecules, such as atypical protein kinase C (aPKC) and Par6 in the follicular epithelium, an effect that can be rescued by overexpression of Crb. Additionally, loss of retromer results in multilayering of the follicular epithelium, indicating that epithelial integrity is severely compromised. Our data reveal a mechanism for Crb trafficking by retromer that is vital for maintaining Crb levels and localization. We also show a novel function for retromer in maintaining epithelial cell polarity.
authors.affiliation: Max Planck Institute for Molecular Cell Biology and Genetics, Pfotenhauerstrasse 108, 01307 Dresden, Germany.
authors.forename: Shirin Meher
authors.initials: SM
authors.lastname: Pocha
authors.forename: Thomas
authors.initials: T
authors.lastname: Wassmer
authors.forename: Christian
authors.initials: C
authors.lastname: Niehage
authors.forename: Bernard
authors.initials: B
authors.lastname: Hoflack
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Knust
mesh_terms: D000818:Animals; D016764:Cell Polarity; D004330:Drosophila / Q000166:cytology / Q000378:metabolism*; D029721:Drosophila Proteins / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D004847:Epithelial Cells / Q000166:cytology* / Q000378:metabolism; D008565:Membrane Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D009154:Mutation; D017434:Protein Structure, Tertiary; D021381:Protein Transport; D034622:RNA Interference; D033921:Vesicular Transport Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism; D021601:trans-Golgi Network / Q000378:metabolism
chemical_list: D029721:Drosophila Proteins; D008565:Membrane Proteins; D033921:Vesicular Transport Proteins; C527271:Vps35 protein, Drosophila; C064360:crb protein, Drosophila