Research Awards
J. Julius Zhu, Ph.D.
University of Virginia
"Aberrant synaptic AMPA-R trafficking in MECP2 knockout mice"
2-Year Award: $100,000
Research Sponsor: Drs. A. Bruce and Daphne Thomas
Final Report (November 2005)
Patients with RTT often have difficult in remembering, talking and behaving appropriately. It is generally believed that the brain learns, remembers, and executes many other cognitive behaviors by controlling the strength of synapses - the connections between neurons. The synaptic strength can be changed due to the movement in and out of synapses of a small number of proteins known as AMPA receptor proteins. Mutations in the MeCP2 protein were recently identified as the primary cause of RTT. But do mutations of MeCP2 cause the aberrant AMPA receptor trafficking and defects in synaptic function? It is now clear that the genetic defects of signaling molecules in small GTPases Ras and Rap signaling pathways can lead to severe mental retardation. Our preliminary results indicate that Ras signaling, which controls synaptic delivery of AMPA receptors, is impaired in Mecp2 knockout mice. Our recent results suggest that impaired synaptic trafficking of AMPA receptors is due primarily to the reduced expression of Ras in Mecp2 knockout mice. We are currently confirming this notion with a variety of experimental approaches combining a number of electrophysiology, imaging, genetics, biochemistry, cell and molecular biology techniques. Identifying the signaling pathway that causes aberrant synaptic function in Mecp2 knockout mice should suggest concrete molecular targets that novel pharmacological and genetic therapies may be developed to treat patients with RTT more efficaciously.
J. Julius Zhu, Ph.D.University of Virginia
"Aberrant synaptic AMPA-R trafficking in MECP2 knockout mice"
2-Year Award: $100,000
Research Sponsor: Drs. A. Bruce and Daphne Thomas
Final Report (November 2005)
Patients with RTT often have difficult in remembering, talking and behaving appropriately. It is generally believed that the brain learns, remembers, and executes many other cognitive behaviors by controlling the strength of synapses - the connections between neurons. The synaptic strength can be changed due to the movement in and out of synapses of a small number of proteins known as AMPA receptor proteins. Mutations in the MeCP2 protein were recently identified as the primary cause of RTT. But do mutations of MeCP2 cause the aberrant AMPA receptor trafficking and defects in synaptic function? It is now clear that the genetic defects of signaling molecules in small GTPases Ras and Rap signaling pathways can lead to severe mental retardation. Our preliminary results indicate that Ras signaling, which controls synaptic delivery of AMPA receptors, is impaired in Mecp2 knockout mice. Our recent results suggest that impaired synaptic trafficking of AMPA receptors is due primarily to the reduced expression of Ras in Mecp2 knockout mice. We are currently confirming this notion with a variety of experimental approaches combining a number of electrophysiology, imaging, genetics, biochemistry, cell and molecular biology techniques. Identifying the signaling pathway that causes aberrant synaptic function in Mecp2 knockout mice should suggest concrete molecular targets that novel pharmacological and genetic therapies may be developed to treat patients with RTT more efficaciously.