The proliferation of Schwann cells is, in part, controlled by interaction with appropriate axons, both in vivo and in vitro. Schwann cells in pure populations in tissue culture remain quiescent unless in contact with axons or membrane fragments derived from axons. We have recently found that the mitogenic response of Schwann cells to the neurites of cultured neurons also occurs when these cells come in contact with PC-12 cells, an established rat pheochromocytoma cell line. This observation provides, for the first time, access to an adequate supply of the neurite mitogen for purification and characterization. We propose to purify the specific protein(s) present on the surface of PC-12 rat phechromocytoma cells which is mitogenic for Schwann cells. Initial observations indicate that the PC-12 mitogen is analogous in function to the mitogen present on the surface of dorsal root ganglia neurites. These mitogens are different from previously identified polypeptide hormones (mitogens), and are presumed to serve to regulate the growth of Schwann cells during normal development. The purified proteins will be characterized and the interaction of these specific growth factors with receptors on the surface of Schwann cells will be studied. The role of 3', 5' cyclic adenosine monophosphate, protein phosphorylation and ion fluxes in the mitogenic response of Schwann cells to these neurite mitogens and to other growth factors, known from previous work to influence Schwann cell proliferation, will be investigated.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
5R01NS019923-05
Application #
3400058
Study Section
Neurological Sciences Subcommittee 1 (NLS)
Project Start
1983-07-01
Project End
1988-06-30
Budget Start
1987-07-01
Budget End
1988-06-30
Support Year
5
Fiscal Year
1987
Total Cost
Indirect Cost
Name
Washington University
Department
Type
Schools of Medicine
DUNS #
062761671
City
Saint Louis
State
MO
Country
United States
Zip Code
63130