| Print Close window |
| Session Information |
|---|
| Session Title: Cytoskeleton and Cellular Biology Session Type: Poster |
| Session Location: Grand Exhibit Hall Session Time: Thursday - Saturday |
| Presentation Information |
| Poster Board Number: 240C Presentation Time: THU 2:00PM-3:00PM, 10:00PM-11:00PM; FRI 8:15PM-9:15PM; SAT 2:30PM-3:30PM; |
| Keywords: KW02e - endocytosis |
| Presentation Content |
|
Rabenosyn and Vps45 regulate cell polarity and early endosomal entry. Holly A. Morrison1, Heather Dionne1, Tor Erik Rusten2, Andreas Brech2, Bill Fisher3, Barret Pfeiffer3, Susan Celniker3, Harald Stenmark2, David Bilder1. 1) Dept of Molecular & Cell Biology, University of California, Berkeley, CA; 2) Centre for Cancer Biomedicine, University of Oslo, and Department of Biochemistry, Institute for Cancer Research, The Norwegian Radium Hospital, Montebello, 0310 Oslo, Norway; 3) Genome Sciences Department, Life Sciences Division, Lawrence Berkeley National Lab, Berkeley, CA. Targeted vesicular trafficking steps are vital for maintaining the proper segregation of intracellular compartments and their protein cargoes. Here we have identified and characterized two important regulators of one of these trafficking steps, Rabenosyn (Rbsn) and Vps45. Rbsn and Vps45 were isolated in a genetic screen for mutations affecting the eye imaginal disc. Cells lacking either of these gene products lose apicobasal polarity and overproliferate, eventually killing the animal. Live trafficking assays demonstrate that endocytosis is defective in these mutant discs; rbsn and Vps45 therefore represent novel endocytic neoplastic tumor suppressor genes. Rbsn localizes to early endosomes and binds to the activated small GTPase Rab5, while Vps45 binds to Rbsn. Vps45 genetically interacts with the syntaxin Avl, suggesting that the target of this protein in Drosophila is a trans-SNARE complex containing Avl. Moreover, TEM analysis indicates that rbsn and vps45 mutant cells have endocytic defects which strongly resemble those seen in avl or rab5 mutants. Our data support a model in which Rbsn localizes to the early endosome via binding to Rab5, recruiting Vps45; Vps45 can then promote vesicle fusion into the early endosome through an interaction with an Avl-containing trans-SNARE complex. This work therefore suggests that Rbsn and Vps45 are part of a tethering complex on early endosomes that links activation of the Rab GTPase to the SNARE fusion machinery. |
| Print Close window |