Molecular Determinants of tGolgin-1 Function
Abstract
TGolgin-l is a large, predominantly coiled coil peripheral membrane protein that associates with the trans Golgi network (rGN) by virtue of a C-terminal GRIP domain. In the first two funding periods, we (1) used a dominant negative expression approach to show that GRIP domain proteins function in endosome to TGN recycling, and (2) used expression ablation with inhibitory RNA to show that tGolgin-1 is specifically required for linking the Golgi complex to microtubule motors. In the last funding period, we focused more specifically on the mechanism by which tGolgin-1 impacts Golgi positioning. We find that tGolgin-1 is required for recycling of a subset of molecules from endosomes to the TGN, in particular glycosphingolipids. Glycosphingolipids are critically important signalling molecules as well as regulators of cholesterol distribution in the cell. In the absence of tGolgin 1, a subset of glycosphingolipids are mistargeted to and accumulated within late endosomes and lysosomes. These data suggest that the primary function of tGolgin-l is in regulating lipid distribution within cells, and that Golgi positioning defects are a consequence of continued defects in glycosphingolipid/ cholesterol distribution. These results imply that altered lipid distribution may impact tumorigenesis in cancer cells that lack tGolgin-i expression.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jul 01, 2004
- Accession Number
- ADA427333
Entities
People
- Atsuko Yoshino
- Mark A. Lemmon
- Michael Marks
Organizations
- University of Pennsylvania