The identification of myosin and its discrete localization in neural tissues has stimulated research focused on a wide variety of possible functions for this protein including growth cone motility, exocytosis, dendritic shape changes and modulation of post- synaptic surface morphology. Neuronal myosin like other nonmuscle myosins may require phosphorylation of its light chain subunits in order to interact with actin and thus generate force. The initial phosphorylation event is therefore critically important in the regulation of the functions which myosin may subserve in neural tissue. We and others have identified several calcium- regulated protein kinases potentially capable of phosphorylating brain myosin, namely type II Ca2+, calmodulin-dependent kinase and myosin light chain kinase (MLCK). In order to explore this regulatory system we propose: 1) to detrmine the immunocytochemical localization of MLCK in the central nervous system, in cultured sympathetic neurons and in isolated brain subcellular fractions, 2) to study the sites and kinetics of the phosphorylation of brain myosin by brain MLCK and type II Ca2+, calmodulin-dependent kinase and 3) to study myosin phosphorylation and its cytoskeletal association in intact nerve endings as functions of depolarization and calcium influx. The results of this research will yield important information about a critical regulatory step in a number of fundamental functions of the neuronal cytoskeleton.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
First Independent Research Support & Transition (FIRST) Awards (R29)
Project #
5R29NS024738-02
Application #
3476820
Study Section
Neurology C Study Section (NEUC)
Project Start
1988-02-01
Project End
1993-01-31
Budget Start
1989-02-01
Budget End
1990-01-31
Support Year
2
Fiscal Year
1989
Total Cost
Indirect Cost
Name
State University of New York at Buffalo
Department
Type
School of Medicine & Dentistry
DUNS #
038633251
City
Buffalo
State
NY
Country
United States
Zip Code
14260