A Drosophila homolog of cyclase-associated proteins collaborates with the Abl tyrosine kinase to control midline axon pathfinding.
We demonstrate that Drosophila capulet (capt), a homolog of the adenylyl cyclase-associated protein that binds and regulates actin in yeast, associates with Abl in Drosophila cells, suggesting a functional relationship in vivo. We find a robust and specific genetic interaction between capt and Abl at the midline choice point where the growth cone repellent Slit functions to restrict axon crossing. Genetic interactions between capt and slit support a model where Capt and Abl collaborate as part of the repellent response. Further support for this model is provided by genetic interactions that both capt and Abl display with multiple members of the Roundabout receptor family. These studies identify Capulet as part of an emerging pathway linking guidance signals to regulation of cytoskeletal dynamics and suggest that the Abl pathway mediates signals downstream of multiple Roundabout receptors.
Wills
Zachary
Z
Department of Cell Biology and Program in Neuroscience, Harvard Medical School, Boston, MA 02115, USA.
Emerson
Mark
M
Rusch
Jannette
J
Bikoff
Jay
J
Baum
Buzz
B
Perrimon
Norbert
N
Van Vactor
David
D
D000818:Animals; D002450:Cell Communication / Q000235:genetics*; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism*; D002454:Cell Differentiation / Q000235:genetics; D002478:Cells, Cultured; D002633:Chemotaxis / Q000235:genetics*; D003598:Cytoskeletal Proteins; D029721:Drosophila Proteins; D004331:Drosophila melanogaster / Q000196:embryology* / Q000235:genetics / Q000648:ultrastructure; D005260:Female; D018507:Gene Expression Regulation, Developmental / Q000235:genetics; D020439:Growth Cones / Q000378:metabolism* / Q000648:ultrastructure; D007150:Immunohistochemistry; D008297:Male; D008840:Microfilament Proteins; D008855:Microscopy, Electron, Scanning; D009154:Mutation / Q000235:genetics; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism; D009420:Nervous System / Q000196:embryology* / Q000378:metabolism / Q000648:ultrastructure; D011505:Protein-Tyrosine Kinases / Q000235:genetics / Q000378:metabolism*; D011971:Receptors, Immunologic / Q000235:genetics / Q000378:metabolism; D000097905:Roundabout Proteins
D018797:Cell Cycle Proteins; D003598:Cytoskeletal Proteins; D029721:Drosophila Proteins; D008840:Microfilament Proteins; D009419:Nerve Tissue Proteins; D011505:Protein-Tyrosine Kinases; D011971:Receptors, Immunologic; C410502:Capt protein, Drosophila; C421243:Robo2 protein, Drosophila; D000097905:Roundabout Proteins; C421244:robo3 protein, Drosophila; C426236:ARG tyrosine kinase