From endomembrane to the plasma membrane: the traffic, signal transduction and micro-localization of H-Ras
Ras proteins are small G proteins that play key roles in many aspect of cell signal transduction. H-Ras is one of three isoforms of mammalian Ras protein that is best studied. The work presented in this dissertation describes how the carboxyl terminal lipid modifications affect the transportation, signal transduction and micro-localizations of H-Ras protein. The already known traffic pathway for H-Ras to the plasma membrane is Golgi mediated classical vesicular Transportation; However, we found the H-Ras transportation has many different features other than the classical pathway, and thereby discovered a new pathway for H-Ras targeting to the plasma membrane. This new pathway is independent of a functional Golgi and is non-vesicular pathway. We also found two H-Ras mutants that are permanently trapped on the endomembranes. By comparing them with the wild type H-Ras, we demonstrated that although these two mutants have similar effector interactions they show distinct biological activities. Finally we studied the micro-localizations of H-Ras protein on the plasma membrane and found the predominant microdomains for H-Ras localization are non-lipid raft microdomains, and this localization is independent of the activation status of H-Ras.*;*This dissertation is a compound document (contains both a paper copy and a CD as part of the dissertation).