COPI coated vesicles (COPI-CVs) are responsible for the retrograde transport of cargo from the Golgi to the endoplasmic reticulum. This research proposal focuses on the two large subunits of the heptameric COPI coat, (3-and yCOP (Sec26p and Sec21p in S. cerevisiae, respectively). These proteins exhibit moderate sequence similarity to one another and very low sequence similarity to the large adaptin subunits of the clathrin coated vesicles; however, the COOH-terminal domain of yCOP has remarkable structural similarity to the adaptin appendages, suggesting conservation of function. The appendage domains of the adaptins play a role in the regulation of vesicle formation via interactions with several partners, and the hypothesis is that the appendage domains of the p and yCOPI proteins may play a similar role. To date, no such regulatory factors have been identified. The goal of this project is to identify the key residues in (3- and yCOP appendage function, as well as to identify potential interacting proteins which may be important in regulation of COPI- CV formation and transport, using yeast as a model. Yeast are an ideal model organism for studying COPI- CV function, as there is considerable conservation compared to mammalian COPI-CVs, in addition to the ease with which experimental manipulations can be carried out in yeast.
| DeRegis, Carol J; Rahl, Peter B; Hoffman, Gregory R et al. (2008) Mutational analysis of betaCOP (Sec26p) identifies an appendage domain critical for function. BMC Cell Biol 9:3 |
