Growth cone neuropilin-1 mediates collapsin-1/Sema III facilitation of antero- and retrograde axoplasmic transport

Collapsin-1/Sema III, a member of the semaphorin family, has been implicate d in axonal path-finding as a repulsive guidance cue. Cellular and molecula r mechanisms by which collapsin-1 exerts its action are not fully understoo d. Collapsin-1 induces growth cone collapse via a pathway which may include neuropilin-1, a cell-surface collapsin-1 binding protein, as well as intra cellular CRMP-62 and heterotrimeric G proteins. We previously identified a second action of collapsin-1, the facilitation of antero- and retrograde ax oplasmic transport. This response occurs via a mechanism distinct from that causing growth cone collapse. To investigate the possible involvement of n europilin-1 in the action of collapsin-1 on axoplasmic transport, we produc ed a soluble neuropilin-1 (sNP-1) lacking the transmembrane and intracellul ar region. sNP-1 progressively displaced the dose-response curve for collap sin-1 eo induce growth cone collapse to higher concentrations, sNP-1 also i nhibited collapsin-1-induced augmentation of both antero- and retrograde ax oplasmic transport. Furthermore, an anti-neuropilin-1 antibody blocked the collapsin-induced axoplasmic transport. These results together indicate tha t neuropilin-1 mediates collapsin-1 action on axoplasmic transport. To visu alize collapsin-1 binding to endogenous neuropilin-1, we used a truncated c ollapsin-1-alkaline phosphatase fusion protein (CAP-4). CAP-4 stains the gr owth cone, neurite, and cell body. However, local application of collapsin- 1 to growth cone but to neither neurite nor cell body promotes axoplasmic t ransport. Thus, growth cone NP-1 mediates the facilitatory action of collap sin-1 on antero- and retrograde axoplasmic transport, (C) 1999 John Wiley & Sons. Inc.