TY - JOUR
T1 - Whacked and Rab35 polarize dynein-motor-complex-dependent seamless tube growth
AU - Schottenfeld-Roames, Jodi
AU - Ghabrial, Amin S.
N1 - Funding Information:
The authors would like to acknowledge: D. Willis, a former Stanford undergraduate student who helped with the rough mapping of wkd; B. Levi, who helped with the third chromosome screen; and M. Krasnow, in whose laboratory the screen and early phases of these studies were carried out. We also thank J. Zhang and the laboratories of M. Scott and H. Bellen (Baylor College of Medicine, USA) for making RabCA and RabDN stocks available to us before publication, the Engels laboratory for sharing deficiency strains, and M. Metzstein (The University of Utah, USA) for sharing 4x-SRF-GAL4 flies. We thank S. DiNardo, C. Burd, E. Bi and members of the Ghabrial and DiNardo laboratories for fruitful discussions. We thank A. S. Burguete, B. Levi and N. Speck for comments on the manuscript. J.S-R. was supported by NIH training grant 5-T32-HD007516-12 and, subsequently, by an NIH postdoctoral fellowship (NRSA—GM090438-01). A.S.G. gratefully acknowledges support from the University of Pennsylvania and the NIH (1R01GM089782-01A1). This work was supported in part by Basil O’Connor Starter Scholar Research Award Grant No. 5-FY09-43 from the March of Dimes Foundation.
PY - 2012/4
Y1 - 2012/4
N2 - Seamless tubes form intracellularly without cell-cell or autocellular junctions. Such tubes have been described across phyla, but remain mysterious despite their simple architecture. In Drosophila, seamless tubes are found within tracheal terminal cells, which have dozens of branched protrusions extending hundreds of micrometres. We find that mutations in multiple components of the dynein motor complex block seamless tube growth, raising the possibility that the lumenal membrane forms through minus-end-directed transport of apical membrane components along microtubules. Growth of seamless tubes is polarized along the proximodistal axis by Rab35 and its apical membrane-localized GAP, Whacked. Strikingly, loss of whacked (or constitutive activation of Rab35) leads to tube overgrowth at terminal cell branch tips, whereas overexpression of Whacked (or dominant-negative Rab35) causes formation of ectopic tubes surrounding the terminal cell nucleus. Thus, vesicle trafficking has key roles in making and shaping seamless tubes.
AB - Seamless tubes form intracellularly without cell-cell or autocellular junctions. Such tubes have been described across phyla, but remain mysterious despite their simple architecture. In Drosophila, seamless tubes are found within tracheal terminal cells, which have dozens of branched protrusions extending hundreds of micrometres. We find that mutations in multiple components of the dynein motor complex block seamless tube growth, raising the possibility that the lumenal membrane forms through minus-end-directed transport of apical membrane components along microtubules. Growth of seamless tubes is polarized along the proximodistal axis by Rab35 and its apical membrane-localized GAP, Whacked. Strikingly, loss of whacked (or constitutive activation of Rab35) leads to tube overgrowth at terminal cell branch tips, whereas overexpression of Whacked (or dominant-negative Rab35) causes formation of ectopic tubes surrounding the terminal cell nucleus. Thus, vesicle trafficking has key roles in making and shaping seamless tubes.
UR - http://www.scopus.com/inward/record.url?scp=84859430314&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84859430314&partnerID=8YFLogxK
U2 - 10.1038/ncb2454
DO - 10.1038/ncb2454
M3 - Article
C2 - 22407366
AN - SCOPUS:84859430314
SN - 1465-7392
VL - 14
SP - 386
EP - 393
JO - Nature cell biology
JF - Nature cell biology
IS - 4
ER -