Growth cone steering by receptor tyrosine phosphatase delta defines a distinct class of guidance cue.
Receptor-type tyrosine phosphatases (RPTPs) are involved in pathfinding decisions by elongating axons, but how they function in these decisions remains unclear. A vertebrate RPTP, PTP-delta, is a neurite-promoting homophilic adhesion molecule; here we demonstrate chemoattraction of CNS growth cones by a locally applied gradient of soluble PTP-delta. The attractive effect of PTP-delta was abolished by inhibition of tyrosine phosphatase activity, but in contrast to other guidance proteins was unaffected by inhibition of cyclic nucleotide activities. Gradients of PTP-delta or of laminin-1 also promoted increases in the speed of growth cone migration, but laminin-1 did not steer growth cones. Our results indicate that PTP-delta is a chemoattractant for vertebrate CNS neurons in vitro and suggest that it represents a distinct class of guidance protein from those previously defined. Further, our data indicate that growth cone attraction is mechanistically distinct from increases in the speed of growth cone movement.
Sun
Q L
QL
Department of Pharmacology, University of Miami School of Medicine, 1600 NW 10 Avenue, Miami, Florida 33136, USA.
Wang
J
J
Bookman
R J
RJ
Bixby
J L
JL
D000818:Animals; D002478:Cells, Cultured; D002642:Chick Embryo; D004791:Enzyme Inhibitors / Q000494:pharmacology; D020439:Growth Cones / Q000187:drug effects* / Q000201:enzymology*; D007797:Laminin / Q000494:pharmacology; D009474:Neurons / Q000201:enzymology / Q000648:ultrastructure; D016548:Prosencephalon / Q000166:cytology; D017027:Protein Tyrosine Phosphatases / Q000235:genetics / Q000494:pharmacology*; D011993:Recombinant Fusion Proteins / Q000494:pharmacology; D014638:Vanadates / Q000494:pharmacology
D004791:Enzyme Inhibitors; D007797:Laminin; D011993:Recombinant Fusion Proteins; C076715:pervanadate; D014638:Vanadates; D017027:Protein Tyrosine Phosphatases