Targeting of Neuronal Proteins
Synaptic
transmission requires spatial assembly of neurotransmitter receptors and
associated signal transduction machinery at synaptic sites and the precise
patterning of dendritic processes. Targeting of proteins to the synapse is a
dynamic process. in which there is a balance of assembly and disassembly of
proteins at synaptic homeostasis. In fact. when learning occurs. recruitment of
existing and newly synthesized proteins to the synapse is increased. In
contrast. when disassembly of synaptic signaling molecules occurs faster than
assembly. homeostasis is lost and disease states such as Alzheimer's Disease
occur in which synaptic transmission is compromised. An important long-term goal
our work is to understand how synaptic targeting of proteins is perturbed in
pathophysiological states.
Our most recent studies focus on dendrite branching. The amount of branches that
a dendrite. or input center of a neuron. contains is thought to be directly
related to learning and memory. In fact. in a number of learning disorders. such
as autism. Rett Syndrome. Down Syndrome. and Alzheimer's Disease. patients show
a reduced number of dendrite branches. These patients also often show
alterations in the metabolism. or breakdown. of a class of compounds called
purines. My laboratory has recently discovered that cypin regulates the number
of dendrite branches in areas of the brain related to learning and memory (Akum
et al.. 2004). We have found that cypin promotes microtubule assembly and that
branching in vivo correlates with cypin's activity as an enzyme involved in
purine metabolism. The ultimate goal would be to be able to develop
pharmaceutical agents to help patients with autism. Rett Syndrome. Down
Syndrome. Alzheimer's Disease and other disorders to increase memory.
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