A SERINE PROTEINASE INVOLVED IN CONTACT MEDIATED REPULSION OF RETINALGROWTH CONES BY DRG NEURITES

Cultured retinal ganglion cell growth cones avoid neurites extending f rom PNS explants. Here we characterize a growth cone collapsing activi ty in detergent extracts of newborn calf adrenal plasma membranes that has characteristics expected for an avoidance cue on peripheral neuri tes. This adrenal derived activity induces the rapid and reversible co llapse of retinal growth cones grown on either of two distinct adhesio n substrata, mouse laminin or the chick cell surface axonal glycoprote in G4/NgCAM. The collapsing activity is inhibited by several different types of serine proteinase inhibitors, including the irreversible inh ibitor 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 b locks the collapse of temporal retinal growth cones on contact with DR G neurites, but does not block the collapse of the same growth cones o n contact with nasal retinal neurites. These results support the hypot hesis that a serine proteinase on peripheral axons serves as an avoida nce cue which induces contact mediated collapse of retinal growth cone s.