Pak1 control of E-cadherin endocytosis regulates salivary gland lumen size and shape.
Generating and maintaining proper lumen size and shape in tubular organs is essential for organ function. Here, we demonstrate a novel role for p21-activated kinase 1 (Pak1) in defining the size and shape of the Drosophila embryonic salivary gland lumen by regulating the size and elongation of the apical domain of individual cells. Pak1 mediates these effects by decreasing and increasing E-cadherin levels at the adherens junctions and basolateral membrane, respectively, through Rab5- and Dynamin-dependent endocytosis. We also demonstrate that Cdc42 and Merlin act together with Pak1 to control lumen size. A role for Pak1 in E-cadherin endocytosis is supported by our studies of constitutively active Pak1, which induces the formation of multiple intercellular lumens in the salivary gland in a manner dependent on Rab5, Dynamin and Merlin. These studies demonstrate a novel and crucial role for Pak1 and E-cadherin endocytosis in determining lumen size and shape, and also identify a mechanism for multiple lumen formation, a poorly understood process that occurs in normal embryonic development and pathological conditions.
BCMB Program of Weill Graduate School of Medical Sciences at Cornell University, New York, NY 10065, USA.
Carolyn
C
Pirraglia
Jenna
J
Walters
Monn Monn
MM
Myat
D000818:Animals; D030801:Animals, Genetically Modified; D015820:Cadherins / Q000378:metabolism*; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism; D004331:Drosophila melanogaster / Q000254:growth & development* / Q000378:metabolism; D034281:Dynamins / Q000235:genetics / Q000378:metabolism; D004705:Endocytosis / Q000235:genetics / Q000502:physiology*; D019204:GTP-Binding Proteins / Q000235:genetics / Q000378:metabolism; D046529:Microscopy, Electron, Transmission; D009154:Mutation; D025581:Neurofibromin 2 / Q000235:genetics / Q000378:metabolism; D012469:Salivary Glands / Q000166:cytology / Q000378:metabolism / Q000648:ultrastructure; D054462:p21-Activated Kinases / Q000235:genetics / Q000378:metabolism*; D020696:rab5 GTP-Binding Proteins / Q000235:genetics / Q000378:metabolism
D015820:Cadherins; C090145:Cdc42 protein, Drosophila; D029721:Drosophila Proteins; D025581:Neurofibromin 2; D054462:p21-Activated Kinases; D019204:GTP-Binding Proteins; D020696:rab5 GTP-Binding Proteins; D034281:Dynamins