Project Detail
Interagency Autism Coordinating Committee (IACC) logo
Office of Autism Research Coordination (OARC) logo

Regulation of synaptogenesis by cyclin-dependent kinase 5  

Mutations in the genes associated with autism appear to disrupt synapse formation, which may account for the social and language impairments as well as the mental retardation often associated with the disorder. CDK5, or cyclin-dependent kinase 5, can regulate the activities of proteins by marking them with phosphate groups. In neurons, loss of CDK5 reduces the electrophysiological response after an activating signal, leading to fewer synapses and impaired learning in mice. The researchers propose that CDK5, Shank 3 and these other proteins participate in a pathway that controls the creation of synapses, and that this pathway may be disrupted in autism. They plan to test this hypothesis by studying how removing CDK5 affects synapse structure and activity. The researchers have developed experimental strategies to study CDK5's role in either the sending or receiving cell of the synapse, and will examine the morphology and electrophysiology of CDK5-deficient neurons. With these experiments, the researchers hope to learn the molecular mechanism of how the kinase regulates synapse formation, which may provide new insights into the role of synapse formation in autism. In particular, they predict that, for proper neuron activity, Shank 3 needs to be phosphorylated by CDK5 at the synapse. If this holds true, targeting phosphorylated Shank 3 to the synapse might improve neurological functioning in people with autism. Project Status
ONGOING

2009

Funder Simons Foundation
Fiscal Year Funding $325,889.25
Project Number 94567
Principal Investigator Tsai, Li-Huei
Received ARRA Funding? No
Strategic Plan Question Question 4: Which Treatments And Interventions Will Help? (Interventions)
Strategic Plan Objective Green dot: Objective has greater than or equal to the recommended funding. 4SB. Standardize and validate at least 20 model systems (e.g., cellular and/or animal) that replicate features of ASD and will allow identification of specific molecular targets or neural circuits amenable to existing or new interventions by 2012. IACC Recommended Budget: $75,000,000 over 5 years.
Federal or Private? Private
Institution Massachusetts Institute of Technology
State/Country Massachusetts
Web Link 1 Regulation of synaptogenesis by cyclin-dependent kinase 5 (External web link)
Web Link 2 No URL available.
Web Link 3 No URL available.
New! History/Related Projects Regulation of synaptogenesis by cyclin-dependent kinase 5 | $342,454.00 | 2010 | 94567