Drosophila Cip4 and WASp define a branch of the Cdc42-Par6-aPKC pathway regulating E-cadherin endocytosis.
BACKGROUND
Integral to the function and morphology of the epithelium is the lattice of cell-cell junctions known as adherens junctions (AJs). AJ stability and plasticity relies on E-Cadherin exocytosis and endocytosis. A mechanism regulating E-Cadherin (E-Cad) exocytosis to the AJs has implicated proteins of the exocyst complex, but mechanisms regulating E-Cad endocytosis from the AJs remain less well understood.


RESULTS
Here we show that Cdc42, Par6, or aPKC loss of function is accompanied by the accumulation of apical E-Cad intracellular punctate structures and the disruption of AJs in Drosophila epithelial cells. These punctate structures derive from large and malformed endocytic vesicles that emanate from the AJs; a phenotype that is also observed upon blocking vesicle scission in dynamin mutant cells. We demonstrate that the Drosophila Cdc42-interacting protein 4 (Cip4) is a Cdc42 effector that interacts with Dynamin and the Arp2/3 activator WASp in Drosophila. Accordingly, Cip4, WASp, or Arp2/3 loss of function also results in defective E-Cadherin endocytosis.


CONCLUSIONS
Altogether our results show that Cdc42 functions with Par6 and aPKC to regulate E-Cad endocytosis and define Cip4 and WASp as regulators of the early E-Cad endocytic events in epithelial tissue.
Leibfried
Andrea
A
Institut CURIE, Centre National de la Recherche, UMR 144, Equipe Polarité Cellulaire chez la Drosophile, 26 rue d'Ulm, 75248 Paris cedex 05, France.
Fricke
Robert
R
Morgan
Matthew J
MJ
Bogdan
Sven
S
Bellaiche
Yohanns
Y
D051376:Actin-Related Protein 2-3 Complex / Q000378:metabolism; D000199:Actins / Q000378:metabolism; D022005:Adherens Junctions / Q000378:metabolism*; D000818:Animals; D015820:Cadherins / Q000378:metabolism*; D002352:Carrier Proteins / Q000378:metabolism; D004330:Drosophila / Q000378:metabolism; D029721:Drosophila Proteins / Q000378:metabolism*; D034281:Dynamins / Q000378:metabolism; D004705:Endocytosis; D004847:Epithelial Cells / Q000378:metabolism; D011493:Protein Kinase C / Q000378:metabolism*; D051316:Wiskott-Aldrich Syndrome Protein / Q000378:metabolism; D020764:cdc42 GTP-Binding Protein / Q000378:metabolism*
D051376:Actin-Related Protein 2-3 Complex; D000199:Actins; D015820:Cadherins; D002352:Carrier Proteins; C534739:Cip4 protein, Drosophila; D029721:Drosophila Proteins; C477859:WASp protein, Drosophila; D051316:Wiskott-Aldrich Syndrome Protein; C115015:PKC-3 protein; C532584:Par-6 protein, Drosophila; D011493:Protein Kinase C; D020764:cdc42 GTP-Binding Protein; D034281:Dynamins