A serine proteinase involved in contact mediated repulsion of retinal growth cones by DRG neurites

Abstract

Cultured retinal ganglion cell growth cones avoid neurites extending from PNS explants. Here we characterize a growth cone collapsing activity in detergent extracts of newborn calf adrenal plasma membranes that has characteristics expected for an avoidance cue on peripheral neurites. This adrenal derived activity induces the rapid and reversible collapse of retinal growth cones grown on either of two distinct adhesion substrata, mouse laminin or the chick cell surface axonal glycoprotein G4/NgCAM. The collapsing activity is inhibited by several different types of serine proteinase inhibitors, including the irreversible inhibitor PPACK (D-phenylalanyl-prolyl-arginine chloromethyl ketone). The activity is not inhibited by the specific thrombin inhibitor, hirudin. We have named the adrenal derived collapsing activity erase. PPACK blocks the collapse of temporal retinal growth cones on contact with DRG neurites, but does not block the collapse of the same growth cones on contact with nasal retinal neurites. These results support the hypothesis that a serine proteinase on peripheral axons serves as an avoidance cue which induces contact mediated collapse of retinal growth cones.