title: Drosophila Cip4/Toca-1 integrates membrane trafficking and actin dynamics through WASP and SCAR/WAVE.
abstract: BACKGROUND
  Developmental processes are intimately tied to signaling events that integrate the dynamic reorganization of the actin cytoskeleton and membrane dynamics. The F-BAR-domain-containing proteins are prime candidates to couple actin dynamics and membrane trafficking in different morphogenetic processes.
  
  
  RESULTS
  Here, we present the functional analysis of the Drosophila F-BAR protein Cip4/Toca1 (Cdc42-interacting protein 4/transducer of Cdc42-dependent actin assembly 1). Cip4 is able to form a complex with WASP and SCAR/WAVE and recruits both actin-nucleation-promoting factors to invaginating membranes and endocytic vesicles. Actin-comet-tail-based movement of these vesicles depends not only on WASP but largely on WAVE function. In vivo, loss of cip4 function causes multiple wing hairs. A similar phenotype is observed when vesicle scission is affected after Dynamin suppression. Gene dosage experiments show that Cip4 and WAVE functionally interact to restrict wing hair formation. Further rescue experiments confirm that Cip4 is able to act through WAVE and WASP in vivo. Biochemical and functional data support a model in which Cdc42 acts upstream of Cip4 and recruits not only WASP but also SCAR/WAVE via Abi to control Dynamin-dependent cell polarization in the wing.
  
  
  CONCLUSIONS
  Cip4 integrates membrane trafficking and actin dynamics through WASP and WAVE. First, Cip4 promotes membrane invaginations and triggers the vesicle scission by recruiting Dynamin to the neck of nascent vesicles. Second, Cip4 recruits WASP and WAVE proteins to induce actin polymerization, supporting vesicle scission and providing the force for vesicle movement.
authors.affiliation: Institut für Neurobiologie, Wilhelms-University Münster, 48149 Münster, Germany.
authors.forename: Robert
authors.initials: R
authors.lastname: Fricke
authors.forename: Christina
authors.initials: C
authors.lastname: Gohl
authors.forename: Elavarasi
authors.initials: E
authors.lastname: Dharmalingam
authors.forename: Astrid
authors.initials: A
authors.lastname: Grevelhörster
authors.forename: Baharak
authors.initials: B
authors.lastname: Zahedi
authors.forename: Nicholas
authors.initials: N
authors.lastname: Harden
authors.forename: Michael
authors.initials: M
authors.lastname: Kessels
authors.forename: Britta
authors.initials: B
authors.lastname: Qualmann
authors.forename: Sven
authors.initials: S
authors.lastname: Bogdan
mesh_terms: D000199:Actins / Q000378:metabolism / Q000502:physiology; D000818:Animals; D001692:Biological Transport; D019521:Body Patterning; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D004330:Drosophila / Q000166:cytology / Q000378:metabolism*; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism* / Q000502:physiology*; D034281:Dynamins / Q000378:metabolism / Q000502:physiology; D004705:Endocytosis; D011992:Endosomes / Q000378:metabolism / Q000502:physiology; D019204:GTP-Binding Proteins / Q000378:metabolism / Q000502:physiology; D018628:Gene Dosage; D008840:Microfilament Proteins / Q000378:metabolism*; D008954:Models, Biological; D014921:Wings, Animal / Q000033:anatomy & histology / Q000254:growth & development; D051316:Wiskott-Aldrich Syndrome Protein / Q000378:metabolism*
chemical_list: D000199:Actins; D002352:Carrier Proteins; C090145:Cdc42 protein, Drosophila; C534739:Cip4 protein, Drosophila; D029721:Drosophila Proteins; D008840:Microfilament Proteins; C449671:SCAR protein, Drosophila; C477859:WASp protein, Drosophila; D051316:Wiskott-Aldrich Syndrome Protein; D019204:GTP-Binding Proteins; D034281:Dynamins