This proposal addresses the molecular control of neuronal cytoskeletal proteins by extracellular signals. The studies proposed here will focus on the regulation and function of the microtubule-associated protein MAP2, a multifunctional neuron-specific protein localized to dendrites. Previous studies under this project established that MAP2 is a multi-functional protein that interacts with both microtubules and actin filaments in a manner regulated by phosphorylation. The continuation of these studies is designed to advance our understanding of MAP2 function by performing detailed analyses of several MAP2-target interactions and their modulation by phosphorylation. High-resolution light microscopy will be used to study the role of MAP2 and its phosphorylated forms in neurite initiation and neuronal growth cone behavior. The mechanism for MAP2's interaction with microtubules and actin filaments will be defined through biochemical analyses. The role of MAP2 as a scaffolding molecule will be examined by combined in vitro and in vivo studies, and novel binding partners for MAP2 will be identified using advanced mass spectroscopy-based approaches. These studies may ultimately identify ways to promote neural regeneration and are fundamentally relevant to several disorders caused by abnormal development or maintenance of neural structure, including mental retardation, neurodegenerative diseases such as Alzheimers, and mental health diseases such as schizophrenia

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
Research Project (R01)
Project #
5R01MH050861-12
Application #
6660715
Study Section
Special Emphasis Panel (ZRG1-MDCN-1 (01))
Program Officer
Asanuma, Chiiko
Project Start
1994-02-01
Project End
2007-07-31
Budget Start
2003-08-01
Budget End
2004-07-31
Support Year
12
Fiscal Year
2003
Total Cost
$416,700
Indirect Cost
Name
Scripps Research Institute
Department
Type
DUNS #
781613492
City
La Jolla
State
CA
Country
United States
Zip Code
92037
Sontag, Jean-Marie; Nunbhakdi-Craig, Viyada; White 3rd, Charles L et al. (2012) The protein phosphatase PP2A/B? binds to the microtubule-associated proteins Tau and MAP2 at a motif also recognized by the kinase Fyn: implications for tauopathies. J Biol Chem 287:14984-93
Dehmelt, Leif; Poplawski, Gunnar; Hwang, Eric et al. (2011) NeuriteQuant: an open source toolkit for high content screens of neuronal morphogenesis. BMC Neurosci 12:100
Malmendal, Anders; Halpain, Shelley; Chazin, Walter J (2003) Nascent structure in the kinase anchoring domain of microtubule-associated protein 2. Biochem Biophys Res Commun 301:136-42