They identified that parkin binds to a protein called endophilin-A, a protein discovered at The Neuro in 1997 by Dr. Peter McPherson, a co-investigator on the current study. Endophilin-A is central to the process of synaptic transmission, specifically synaptic vesicle trafficking. Synaptic transmission is the process whereby one nerve cell communicates with another. It involves the release of neurotransmitters from a synaptic vesicle at the surface of the cell. The neurotransmitter travels across the gap or synapse and is brought into (or endocytosed) the communicating neuron. Synaptic vesicles are spheres that transport and release neurotransmitters, the 'signal' required for the propagation of nerve cell signals across the synapse. The binding protein, endophilin-A plays an important role in regulating synaptic vesicle endocytosis, that is the formation, as well as recycling of synaptic vesicles.
"One of the most consistent and intriguing findings associated with both dominant and recessive forms of Parkinson's, including those due to parkin mutations, have been defects in synaptic transmission, possibly related to altered synaptic vesicle endocytosis, recycling or release," says Dr. Fon. "Yet, until now, the molecular mechanisms involved have remained completely unknown. Thus, by linking parkin to endophilin-A, a protein at the heart of synaptic vesicle endocytosis and recycling, our findings provide a molecular link between recessive Parkinson's genes and defects in synaptic transmission. This now gives us a whole new set of potential treatment targets."
"This provides a novel and critical molecular link between the parkin gene and synaptic regulation," says Dr. Jean-Francois Trempe, post-doctoral student in Dr. Kalle Gehring's lab at McGill, who studied the structural biology of the binding of the two proteins."The strength and
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