Molecular Determinants of tGolgin-1 Function
Abstract
TGolgin-1 is a large, predominantly coiled coil peripheral membrane protein that associates with the trans Golgi network (TGN) by virtue of a C-terminal GRIP domain. We showed that overexpression of isolated GRIP domains from tGolgin- 1 or related proteins results in disruption of the TGN by inhibiting recycling from endosomes, suggesting that tGolgin-l and other GRIP domain proteins function in this pathway. This is important because signalling molecules required for initiating transformation and for metastasis rely on sorting and processing in the TGN. In collaboration with Dr. Chris Burd, we showed that GRIP domain localization to the TGN in yeast is regulated by a small GTPase cascade, in which the Arf-like protein Ar13 recruits the Arf-like protein Ar11, and activated Ar11 in turn binds directly to and recruits GRIP domains. Orthologues of these proteins function similarly in mammalian cells. Using RNAi to ablate expression of tGolgin-1 from mammalian cells, we have shown that tGolgin-1 also participates in the association of the Golgi complex to the dynein/dynactin complex. This has important implications for a role of tGolgin-l in cell motility and polarization required for tumor development, metastasis, and immunity. We are now probing for the mechanism of this function of tGolgin- 1.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jul 01, 2003
- Accession Number
- ADA418143
Entities
People
- Atsuko Yoshino
- Mark A. Lemmon
- Michael Marks
Organizations
- University of Pennsylvania