The goal is to elucidate some of the mechanisms that control the formation of neuronal networks during development and regeneration. The studies are focused on the role that membrane components of the nerve growth cone play in these mechanisms. Of particular interest are: (i) the insertion of specific membrane components, the sodium channel and a growth-associated protein, into specific plasmalemmal domains of the growing neuron, (ii) the nature and variability of membrane glycoproteins of the growth cone, (iii) the molecular characteristics of an N-CAM-like, growth-associated glycoprotein, (iv) the nature and variability of membrane glycolipids of the growth cone, and (iv) the appearance of specific membrane components at the nerve terminal during synaptogenesis. The proposed studies make use of a wide range of morphological, biochemical and immunological techniques as well as of tissue culture and subcellular fractionation. This work is expected to lead to new insights into the molecular mechanisms of growth-cone - target-cell interaction and synaptogenesis. Such knowledge will form the basis for studies on the causes of developmental and degenerative disorders of the CNS and for our understanding of regeneration in the CNS.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
5R01NS024676-04
Application #
3409475
Study Section
Neurology C Study Section (NEUC)
Project Start
1986-12-01
Project End
1991-11-30
Budget Start
1989-12-01
Budget End
1990-11-30
Support Year
4
Fiscal Year
1990
Total Cost
Indirect Cost
Name
University of Colorado Denver
Department
Type
Schools of Medicine
DUNS #
065391526
City
Aurora
State
CO
Country
United States
Zip Code
80045
DeBin, J A; Wood, M R; Pfenninger, K H et al. (1994) A chloride channel reconstituted from fetal rat brain growth cones. J Membr Biol 141:7-19
Quiroga, S; Pfenninger, K H (1994) Characterization of gp93, a novel, highly heterogeneous glycoprotein present in growth cone membranes. J Neurochem 63:1150-8
Pfenninger, K H; Friedman, L B (1993) Sites of plasmalemmal expansion in growth cones. Brain Res Dev Brain Res 71:181-92
Alcantara, A A; Pfenninger, K H; Greenough, W T (1992) 5B4-CAM expression parallels neurite outgrowth and synaptogenesis in the developing rat brain. J Comp Neurol 319:337-48
Wallis, I; Lasher, R S; Ellis, L et al. (1992) A developmentally regulated plasmalemmal antigen present in synaptosomes but not in growth cones. Brain Res Dev Brain Res 67:265-78
Wood, M R; DeBin, J; Strichartz, G R et al. (1992) Plasmalemmal insertion and modification of sodium channels at the nerve growth cone. J Neurosci 12:2948-59
Li, H N; Quiroga, S; Pfenninger, K H (1992) Variable membrane glycoproteins in different growth cone populations. J Neurosci 12:2393-402
Pfenninger, K H; de la Houssaye, B A; Helmke, S M et al. (1991) Growth-regulated proteins and neuronal plasticity. A commentary. Mol Neurobiol 5:143-51
Sbaschnig-Agler, M; Pfenninger, K H; Ledeen, R W (1988) Gangliosides and other lipids of the growth cone membrane. J Neurochem 51:212-20