Abstract

This research is aimed at elucidating the molecular mechanisms that control axonal growth and regeneration in the CNS. Second-messenger systems activated by putative growth factor(s) are to be analyzed and such factor(s) purified. The main experimental systems to be used are nerve growth cone fragments (GCPs) isolated from fetal rat brain and cultures of fetal rat cerebral cortex. In the coming year, the following studies will be performed: 1) The further purification and characterization of a peptide factor activating polyphosphoinositide cleavage in CNS growth cones. 2) Analysis of the effects of this putative growth factor on protein phosphorylation in the growth cone. 3) Analysis of the involvement of this peptide factor, of phosphoinositide metabolism, Ca2+, and protein kinase C in the regulation of growth cone motility, using localized application of appropriate agents to neurons sprouting in culture and video-microscopy. 4) Further characterization of membrane protien pp46, a major substrate of a Ca2+/calmodulin-dependent kinase and protein kinase C.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
5R01NS024672-04
Application #
3409463
Study Section
Neurology B Subcommittee 1 (NEUB)
Project Start
1986-07-01
Project End
1991-12-31
Budget Start
1989-01-01
Budget End
1989-12-31
Support Year
4
Fiscal Year
1989
Total Cost
Indirect Cost

  Institution

Name
University of Colorado Denver
Department
Type
Schools of Medicine
DUNS #
065391526
City
Aurora
State
CO
Country
United States
Zip Code
80045

  Publications

Pfenninger, Karl H; Laurino, Lisandro; Peretti, Diego et al. (2003) Regulation of membrane expansion at the nerve growth cone. J Cell Sci 116:1209-17
Mikule, Keith; Gatlin, Jesse C; de la Houssaye, Becky A et al. (2002) Growth cone collapse induced by semaphorin 3A requires 12/15-lipoxygenase. J Neurosci 22:4932-41
Ross, S; Essary, B; de la Houssaye, B A et al. (2000) Thrombin causes pseudopod detachment via a pathway involving cytosolic phospholipase A2 and 12/15-lipoxygenase products. Cell Growth Differ 11:19-30
de La Houssaye, B A; Mikule, K; Nikolic, D et al. (1999) Thrombin-induced growth cone collapse: involvement of phospholipase A(2) and eicosanoid generation. J Neurosci 19:10843-55
Helmke, S; Lohse, K; Mikule, K et al. (1998) SRC binding to the cytoskeleton, triggered by growth cone attachment to laminin, is protein tyrosine phosphatase-dependent. J Cell Sci 111 ( Pt 16):2465-75
Mascotti, F; Caceres, A; Pfenninger, K H et al. (1997) Expression and distribution of IGF-1 receptors containing a beta-subunit variant (betagc) in developing neurons. J Neurosci 17:1447-59
Negre-Aminou, P; Nemenoff, R A; Wood, M R et al. (1996) Characterization of phospholipase A2 activity enriched in the nerve growth cone. J Neurochem 67:2599-608
Lohse, K; Helmke, S M; Wood, M R et al. (1996) Axonal origin and purity of growth cones isolated from fetal rat brain. Brain Res Dev Brain Res 96:83-96
Quiroga, S; Garofalo, R S; Pfenninger, K H (1995) Insulin-like growth factor I receptors of fetal brain are enriched in nerve growth cones and contain a beta-subunit variant. Proc Natl Acad Sci U S A 92:4309-12
Negre-Aminou, P; Pfenninger, K H (1993) Arachidonic acid turnover and phospholipase A2 activity in neuronal growth cones. J Neurochem 60:1126-36

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