Role of the signaling GTPase dynamin in coordinating endocytosis with other cellular functions to maintain homeostasis. That is, as a vesicle (small bubble enclosed by cells lipid bilayer) invaginates, dynamin forms a spiral around the neck of the vesicle. Once the spiral is in place, it extends lengthwise and constricts through GTP hydrolysis. This lengthening and tightening of the coil around the vesicle neck causes it to break and results in the pinching off of the vesicle from the parent membrane.
Our research aims at the biochemical characterization of recently identified mutations within dynamin that have been associated with neuromuscular diseases.
My research and others have provided further evidence that dynamin is multi-functional, with the potential to regulate diverse aspects of cellular function: The isoform dynamin-2 is associated with selective sites of actin rearrangements where it recruits proteins known to regulate actin assembly. We provided one of the first lines of evidence that dynamin-2 specifically acts as a signaling component that controls entry into an apoptosis pathway. Dynamin-2, but not dynamin-1, can induce apoptosis when expressed as little as 2-fold over the endogenous level. This response is dependent on the presence of functional p53, a tumor suppressor and transcriptional regulator, suggesting a role for dynamin as signaling GTPase in response to cell stress. My goal is to use this dynamin-2 specific phenotype to understand how this multi-functional enzyme links endocytic events to signal transduction, rearrangements of the actin cytoskeleton, cell proliferation and apoptosis. With cell biological, biochemical and profiling approaches we will gain valuable insights into these fundamental questions relevant to cancer biology.
