Journal of Neuroscience, Vol 7, 2664-2673, Copyright © 1987 by Society for Neuroscience
Characterization of an inhibitor of neuronal plasminogen activator released by heart cells
RN Pittman and PH Patterson
A basic understanding of growth cone dynamics and developmental events
involving growth cones requires an understanding of the function and
regulation of molecules associated with and released by growth cones. Rat
sympathetic neurons in culture release a urokinase-like plasminogen
activator from their distal processes and/or growth cones (Pittman, 1985a).
When sympathetic neurons are grown in cocultures with heart cells, however,
plasminogen activator activity is not detected. The absence of plasminogen
activator activity in cocultures of sympathetic neurons and heart cells
appears to be due to the release of an inhibitor of plasminogen activator
by heart cells. This inhibitor has a molecular weight of approximately 50
kDa in the presence of SDS and apparent molecular weights of approximately
50 and greater than 2000 kDa under native conditions. A significant
fraction of the large- molecular-weight form of the inhibitor is converted
to the smaller form following treatment with heparinase. Extremely stable
complexes of 68 and 80 kDa are formed between the heart inhibitor and the
plasminogen activator, urokinase, such that the complexes withstand boiling
in SDS/mercaptoethanol. The data are consistent with the formation of an 80
kDa urokinase-inhibitor complex in the presence of heparan sulfate
proteoglycan and a 68 kDa complex in the absence of heparan sulfate
proteoglycan. A highly purified preparation of the heart inhibitor produces
a 2- to 3-fold increase in neurite outgrowth from sympathetic neurons.
These data indicate that the activity of the plasminogen activator released
by sympathetic neurons can be regulated by a normal target tissue and that
this regulation may result in increased neurite outgrowth from the neurons.