Growth cone steering by receptor tyrosine phosphatase delta defines a distinct class of guidance cue

Mol Cell Neurosci. 2000 Nov;16(5):686-95. doi: 10.1006/mcne.2000.0893.

Abstract

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.

Publication types

  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Cells, Cultured
  • Chick Embryo
  • Enzyme Inhibitors / pharmacology
  • Growth Cones / drug effects*
  • Growth Cones / enzymology*
  • Laminin / pharmacology
  • Neurons / enzymology
  • Neurons / ultrastructure
  • Prosencephalon / cytology
  • Protein Tyrosine Phosphatases / genetics
  • Protein Tyrosine Phosphatases / pharmacology*
  • Recombinant Fusion Proteins / pharmacology
  • Vanadates / pharmacology

Substances

  • Enzyme Inhibitors
  • Laminin
  • Recombinant Fusion Proteins
  • pervanadate
  • Vanadates
  • Protein Tyrosine Phosphatases