Newer Methods Drive Recent Insights into Rab GTPase Biology: An Overview.

The conserved Ypt/Rab GTPases regulate all major intracellular protein traffic pathways, including secretion, endocytosis and autophagy. These GTPases undergo distinct changes in conformation between their GTP- and GDP-bound forms and cycle between the cytoplasm and membranes with the aid of their upstream regulators. When activated on the membrane in the GTP-bound form, they recruit their downstream effectors, which include components of vesicular transport. Progress in the past 5 years regarding mechanisms of Rab action, functions, and the effects of disruption of these functions on the well-being of cells and organisms has been propelled by advances in methodologies in molecular and cellular biology. Here, we highlight methods used recently to analyze regulation, localization, interactions, and function of Rab GTPases and their roles in human disease. We discuss contributions of these methods to new insights into Rabs, as well as their future use in addressing open questions in the field of Rab biology.