The influence of surface protease activity on neuritogenesis and neurite retraction is dependent upon mode of neurite induction: Inhibition of thrombin-mediated surface protease activity is cruicial for neurite outgrowth but not for maintenance of existin

Previous studies have shown that thrombin prevents neurite outgrowth and induces neurite retraction in some but not all neuroblastoma lines. In the present study, cells were induced to elaborate neurites by serum deprivation. Alternate cultures were treated to induce alterations in those kinase activities known to induce neurite outgrowth and to enhance deposition into neurites of stabilizing cytoskeletal consituents such as phosphorylated neurofilaments. The relative influence of thrombin on neurites generated under these various conditions was examined. Quantitation of neurite length as a function of somal diameter revealed shortening, but not complete retraction, of neurites under all conditions. However, the relative percentage of neurites that underwent thrombin-induced shortening was substantially reduced in cultures deprived of serum in combination with alteration of kinase activities. Neurite reduction, rather than complete elimination, indicates that the influence of thrombin on neurites may be relatively confined to the distal end of elaborating neurites, and that the deposition of certain cytoskeletal consituents may progressively lessen the requirement of developing neurites on (thrombin-mediated) surface protease inhibition. These findings further suggest that, even during relatively early stages in neuritogenesis, thrombin-mediated surface protease activity exerts a greater influence on neurite initiation and elongation rather than maintenance of existing neurites.