Dynamin 1 Gene Critical for Sophisticated Brain Function

Pietro DeCamilli

New Haven, Conn. — A gene found exclusively and at high levels in the brain appears to be a key player in enabling more sophisticated brain function, Yale School of Medicine researchers report in Science.

The finding about the gene, dynamin 1, could have widespread implications since members of the dynamin gene family are needed for the body to absorb nutrients, to grow, to respond to insulin, and even for viruses to gain entry into cells.

“We envision that the lessons we learn about the role of dynamin 1 may prove widely applicable to understanding the biology of many cell types in both healthy states and disease states,” said Pietro DeCamilli, professor of cell biology and neurobiology, Howard Hughes Medical Institute Investigator, and senior author of the study.

Dynamin encodes a protein implicated in endocytosis, which is when cells absorb material from the outside by engulfing it with their cell membranes. There has been considerable evidence that dynamin 1 is required for a specialized form of endocytosis in brain cells that is responsible for generating the synaptic vesicles that store and release neurotransmitter.

To test this hypothesis, DeCamilli and his colleagues disrupted the dynami 1 gene in mice and found, to their surprise, that the mice developed normally up until the time of birth. They were initially able to move and feed just like the other mice. Only subsequently did the mutant mice develop neurological impairments and a failure to thrive that led to death within two weeks after birth.

“It was quite striking that their nervous system could support synaptic transmission in the absence of dynamin 1, which is by far the major brain dynamin,” DeCamilli said.

Shawn Ferguson, a postdoctoral fellow in the lab and first author of the study, said detailed functional and ultrastructural analysis of mutant synapses revealed that synaptic vesicles can re-form in the absence of dynamin 1. “This protein becomes essential for synaptic vesicle endocytosis and recycling only under conditions of intense synaptic activity,” he said.

DeCamilli said the properties of dynamin 1 and its binding partners that make them optimally adapted to function in the context of a simulated synapse are being investigated. It is expected that these studies will reveal new important features of synaptic physiology.

Science: (April 26, 2007)

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