The project seeks to understand the functions of cytoplasmic motors in neurons in order to understand fast and slow axonal transport. New types of myosin motors attached to the surfaces of squid axonal organelles now appear to belong to at least two species of myosin. We have developed antibodies to various nervous system myosins to determine which myosins move organelles. Potential organelle myosins are now being sequenced and probes developed to explore their role in axonal transport. New studies of the organization of the actin substrates for these motors in the axon have shown that parallel actin filaments intertwine with the microtubule bundles, and that they have mixed polarities, suggesting that they might carry organelles to and from the microtubule bundles. Regarding slow axonal transport, negatively charged macomolecular assemblies injected into the squid giant axon move in the anterograde direction at rates up to 0.5 um/sec. Of particular interest is that neurofilament proteins as well as actin and microtubule fragments move anterogradely, and that these movements appear to be along some type of intracellular tract. Recent results suggest that these tracts are microtubule bundles and that the motors come from the soluble pools of conventional kinesin. Indeed, depolymerizing the axonal microtubules blocks slow neurofilament transport.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Intramural Research (Z01)
Project #
1Z01NS002551-17
Application #
6111841
Study Section
Special Emphasis Panel (LN)
Project Start
Project End
Budget Start
Budget End
Support Year
17
Fiscal Year
1998
Total Cost
Indirect Cost
City
State
Country
United States
Zip Code
Galbraith, Catherine G; Yamada, Kenneth M; Galbraith, James A (2007) Polymerizing actin fibers position integrins primed to probe for adhesion sites. Science 315:992-5
Colina, Claudia; Rosenthal, Joshua J C; DeGiorgis, Joseph A et al. (2007) Structural basis of Na(+)/K(+)-ATPase adaptation to marine environments. Nat Struct Mol Biol 14:427-31
Satpute-Krishnan, Prasanna; DeGiorgis, Joseph A; Conley, Michael P et al. (2006) A peptide zipcode sufficient for anterograde transport within amyloid precursor protein. Proc Natl Acad Sci U S A 103:16532-7
DeGiorgis, Joseph A; Reese, Thomas S; Bearer, Elaine L (2002) Association of a nonmuscle myosin II with axoplasmic organelles. Mol Biol Cell 13:1046-57
Galbraith, J A; Reese, T S; Schlief, M L et al. (1999) Slow transport of unpolymerized tubulin and polymerized neurofilament in the squid giant axon. Proc Natl Acad Sci U S A 96:11589-94