title: Cooperative functions of the two F-BAR proteins Cip4 and Nostrin  in the regulation of E-cadherin in epithelial morphogenesis.
abstract: F-BAR proteins are prime candidates to regulate membrane curvature and dynamics during different developmental processes. Here, we analyzed nostrin, a so-far-unknown Drosophila melanogaster F-BAR protein related to Cip4. Genetic analyses revealed a strong synergism between nostrin and cip4 functions.Whereas single mutant flies are viable and fertile, combined loss of nostrin and cip4 results in reduced viability and fertility. Double mutant escaper flies show enhanced wing polarization defects and females exhibit strong egg chamber encapsulation defects. Live imaging analysis suggests that the observed phenotypes are caused by an impaired turnover of E-cadherin at the membrane. Simultaneous knockdown of Cip4 and Nostrin strongly increases the formation of tubular E-cadherin vesicles at adherens junctions. Cip4 and Nostrin localize at distinct membrane subdomains. Both proteins prefer similar membrane curvatures but seem to form distinct membrane coats and do not heterooligomerize. Our data suggest an important synergistic function of both F-BAR proteins in membrane dynamics. We propose a cooperative recruitment model, in which Cip4 initially promotes membrane invagination and early-actin-based endosomal motility, and Nostrin makes contacts with microtubules through the kinesin Khc-73 for trafficking of recycling endosomes.
authors.forename: Thomas
authors.initials: T
authors.lastname: Zobel
authors.forename: Klaus
authors.initials: K
authors.lastname: Brinkmann
authors.forename: Nicole
authors.initials: N
authors.lastname: Koch
authors.forename: Katharina
authors.initials: K
authors.lastname: Schneider
authors.forename: Eric
authors.initials: E
authors.lastname: Seemann
authors.forename: Astrid
authors.initials: A
authors.lastname: Fleige
authors.forename: Britta
authors.initials: B
authors.lastname: Qualmann
authors.forename: Michael M
authors.initials: MM
authors.lastname: Kessels
authors.forename: Sven
authors.initials: S
authors.lastname: Bogdan
mesh_terms: D022005:Adherens Junctions / Q000378:metabolism; D000818:Animals; D015820:Cadherins / Q000378:metabolism*; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D002454:Cell Differentiation; D002460:Cell Line; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism*; D004331:Drosophila melanogaster / Q000196:embryology / Q000235:genetics; D004705:Endocytosis / Q000235:genetics / Q000502:physiology; D011992:Endosomes / Q000378:metabolism; D004847:Epithelial Cells / Q000166:cytology; D016547:Kinesins / Q000378:metabolism; D008869:Microtubule-Associated Proteins / Q000235:genetics / Q000378:metabolism*; D008870:Microtubules / Q000378:metabolism*; D009024:Morphogenesis / Q000502:physiology; D010063:Ovum / Q000502:physiology*; D021381:Protein Transport / Q000502:physiology; D034622:RNA Interference; D034741:RNA, Small Interfering; D014921:Wings, Animal / Q000196:embryology*
chemical_list: D015820:Cadherins; D002352:Carrier Proteins; C534739:Cip4 protein, Drosophila; D029721:Drosophila Proteins; C104644:Khc-73 protein, Drosophila; D008869:Microtubule-Associated Proteins; C000606137:Nost protein, Drosophila; D034741:RNA, Small Interfering; D016547:Kinesins