| Members of the dynamin superfamily of large GTPases are known to participate in diverse cellular processes, including endocytosis, mediation of antiviral resistance, midzone formation during cytokinesis, as well as both fission and fusion of mitochondria. The ability of these GTPases to undergo nucleotide-regulated self-assembly appears to be critical for their physiological function, and is encoded in the conserved GTPase, middle and GTPase effector domains. The goal of this thesis is to understand how GTP hydrolysis is coupled, through unique targeting and effector domains, to the cellular functions of these dynamin-like proteins. I first focus specifically on the role of phosphoinositide binding by the dynamin PH domain during dynamin-dependent endocytosis. My data indicate that the dynamin PH domain does not act in targeting of this GTPase to its site of action, but is instead required as an effector module during vesicle scission. Next I present my finding that the related protein MxB can regulate nuclear import, in part via interactions mediated by its unique amino-terminal extension. Finally, I demonstrate that a unique region of Drp1, a mitochondrial fission protein, functions as an independent targeting and/or effector module. |
