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Study revises dynamin's role in nerve cell function

hila fruit fly established dynamin 1's role in this vesicle recycling process," Dr. Ryan explains. "Essentially, the enzyme undergoes a chemical change whereby it physically squeezes off a piece of the old vesicular membrane -- creating a brand new vesicle poised to take on a new load of neurotransmitter."

Based on this work in fruit flies, neuroscientists had assumed that dynamin 1 was necessary for the growth and function of all synaptic transmission.

But Dr. Ryan, along with co-senior author Dr. Pietro De Camilli, a Howard Hughes Medical Institute investigator and professor of cell biology at Yale, decided to test that notion.

Dr. De Camilli's laboratory in New Haven had worked hard to develop a unique, genetically engineered mouse without dynamin 1. If the enzyme was essential to all synaptic activity, these mice would die very soon after birth.

But the pups were born, and initially appeared healthy. "That was the really big surprise here," Dr. Ryan says. "Pups lacking dynamin 1 moved and suckled just like normal pups at birth."

Lab study revealed that synaptic activity in these mice was functioning at a low level -- enough to keep the mice alive over the short term -- without dynamin 1.

"The enzyme's function appears to be much more subtle than we had imagined," Dr. Ryan says. "It may not be necessary under conditions of low synaptic activity. In those cases, we suspect that other related enzymes, such as dynamin 2 and 3, may shoulder the load and carry out some residual function."

"But as soon as cells require higher levels of synaptic activity, dynamin 1 becomes absolutely necessary," he says.

Normal growth and function demand that neurons work at high capacity, so young mice without dynamin 1 eventually did die off, usually within a week or two of birth.

"These findings really change our outlook on dynamin 1, and on synaptic vesicle endocytosis in general," Dr. Ryan say
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Contact: Andrew Klein
ank2017@med.cornell.edu
212-821-0560
New York- Presbyterian Hospital/Weill Cornell Medical Center/Weill Cornell Medical College
11-May-2007


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