Protein key to trafficking in nerve terminals

July 22, 2004

A protein characterized by researchers at Baylor College of Medicine plays an important role in communication between neurons. This protein is overactive (up-regulated) in children with Down's Syndrome.

Identifying this protein - Dap160 — and its function is an important step in understanding how neurons communicate with one another, said Dr. Hugo Bellen, BCM professor of molecular and human genetics, a Howard Hughes Medical Institute investigator, and director of the program in developmental biology. The report appears in the July 22, 2004, issue of the journal Neuron.

Dap 160 was found as part of a new screen developed in Bellen's laboratory. The screen revealed many genes involved in neuronal function and development, said Bellen. Dap160 stands for Dynamin-associated protein of 160 kD (kilodaltons). Dynamin is a protein that is crucial to the final portion of the synaptic process.

Neurotransmitters are the chemicals that contain the message to be transmitted when neurons talk to each other or to other cells. These chemicals are contained in small vesicles inside nerve endings called synapses.

When a nerve pulse invades the nerve ending, these vesicles fuse with the membrane at the tip of the nerve ending (called the synaptic membrane). At this point, vesicles release their contents so that a nearby cell receives the message.

"You need to retrieve the vesicles at the synapse to maintain a constant supply of vesicles in the nerve terminal," said Bellen. At least two distinct types of vesicle retrieval occur at the synapse, but the most well studied mechanism of vesicle retrieval is based on retrieving little pieces of membrane from the synaptic membrane. As the vesicles start to bud off the cell membrane, dynamin accumulates on the vesicle. The role of this protein is still controversial, Bellen said. Some people think it's a "pinchase," pinching the vesicle off the cell membrane. Others think that it recruits other proteins to help pinching off the vesicle.

When Dap160, which binds dynamin, is removed from the vesicle retrieval process, the pinching-off either does not occur properly, or occurs too late. As a result, the vesicle keeps growing and subsequently becomes loaded with too much neurotransmitter. Bellen and his colleagues believe that Dap160 stabilizes the complex of molecules involved in the retrieval and formation of vesicles, allowing for neurotransmitters to be released in a continuous fashion.

"Besides budding from the membrane, there is at least one other form of vesicle retrieval at the synapse", Bellen said. A rapid retrieval mechanism called "kiss and run" occurs when the vesicle fuses with the membrane but the vesicle membrane does not collapse into the synaptic membrane. Rather, kiss and run vesicles release neurotransmitters through a pore in the membrane. The vesicles are then retrieved by pinching of the fusion pore at the site of release. These vesicles stay close to release sites and are reused immediately.

Interestingly, Dap160 is not only involved in retrieving vesicles from the membrane, but it is also implicated in kiss and run type vesicle recycling. This has important implications for the regulation of vesicle retrieval mechanisms at the synapse, Bellen said.
-end-
The main authors of the study are Tong-Wey Koh and Patrik Verstreken, both associated with BCM.

Baylor College of Medicine

Related Neurons Articles from Brightsurf:

Paying attention to the neurons behind our alertness
The neurons of layer 6 - the deepest layer of the cortex - were examined by researchers from the Okinawa Institute of Science and Technology Graduate University to uncover how they react to sensory stimulation in different behavioral states.

Trying to listen to the signal from neurons
Toyohashi University of Technology has developed a coaxial cable-inspired needle-electrode.

A mechanical way to stimulate neurons
Magnetic nanodiscs can be activated by an external magnetic field, providing a research tool for studying neural responses.

Extraordinary regeneration of neurons in zebrafish
Biologists from the University of Bayreuth have discovered a uniquely rapid form of regeneration in injured neurons and their function in the central nervous system of zebrafish.

Dopamine neurons mull over your options
Researchers at the University of Tsukuba have found that dopamine neurons in the brain can represent the decision-making process when making economic choices.

Neurons thrive even when malnourished
When animal, insect or human embryos grow in a malnourished environment, their developing nervous systems get first pick of any available nutrients so that new neurons can be made.

The first 3D map of the heart's neurons
An interdisciplinary research team establishes a new technological pipeline to build a 3D map of the neurons in the heart, revealing foundational insight into their role in heart attacks and other cardiac conditions.

Mapping the neurons of the rat heart in 3D
A team of researchers has developed a virtual 3D heart, digitally showcasing the heart's unique network of neurons for the first time.

How to put neurons into cages
Football-shaped microscale cages have been created using special laser technologies.

A molecule that directs neurons
A research team coordinated by the University of Trento studied a mass of brain cells, the habenula, linked to disorders like autism, schizophrenia and depression.

Read More: Neurons News and Neurons Current Events
Brightsurf.com is a participant in the Amazon Services LLC Associates Program, an affiliate advertising program designed to provide a means for sites to earn advertising fees by advertising and linking to Amazon.com.