THE LEECH RECEPTOR PROTEIN-TYROSINE-PHOSPHATASE HMLAR2 IS CONCENTRATED IN GROWTH CONES AND IS INVOLVED IN-PROCESS OUTGROWTH

Developing neurons extend long processes to specific distal targets us ing extracellular molecules as guidance cues to navigate through the e mbryo. Growth cones, specialized structures at the tip of the extendin g processes, are thought to accomplish this navigation through recepto rs that recognize guidance cues and modulate growth accordingly. In Dr osophila, several receptor tyrosine phosphatases (rPTPs), including DL AR, hare been shown to participate in directing neurite outgrowth. As yet, however, it is not known how rPTPs act to affect navigation. To g ain insight into the mechanisms of rPTP-mediated outgrowth guidance, w e have investigated the role of HmLAR2, a Hirudo medicinalis homologue of DLAR, in process outgrowth. HmLAR2 is expressed by, among other ce lls, a transient neuron-like template cell, the Comb cell. Here we pre sent evidence that HmLAR2 protein becomes concentrated within their gr owth cones at a stage when C cell processes undergo rapid outgrowth, W hen antibodies raised against the extracellular domain of HmLAR2 were injected into intact embryos, they bound specifically to the C cell su rface at growth cones and along processes and caused the partial inter nalization of HmLAR2 receptors, Moreover, the C cell processes were fo und to project aberrantly, to deviate from their normally highly regul ar trajectories and to extend shorter distances in the presence of the antibodies. We propose that HmLAR2 is required by the C cell for guid ance and extension and suggest that it functions via its ectodomain to transduce extracellular guidance cues.