Thrombin receptor activation causes rapid neural cell rounding and neurite retraction independent of classic second messengers

J Cell Biol. 1992 Jul;118(2):411-9. doi: 10.1083/jcb.118.2.411.


The protease thrombin is a potent activator of various cell types. Thrombin cleaves and thereby activates its own seven-transmembrane-domain receptor which couples to G proteins. Thrombin also can inhibit neuronal differentiation, supposedly by degrading components of the extracellular matrix. Here we report that active thrombin induces immediate cell rounding and neurite retraction in differentiating N1E-115 and NG108-15 neural cells in serum-free culture. Serum (0.5-5% vol/vol) evokes similar responses, but the cell-rounding and neurite-retracting activity of serum is not attributable to thrombin. Neural cell rounding is transient, subsiding after 10-15 min, and subject to homologous desensitization, whereas retracted neurites rapidly degenerate. Thrombin action is inhibited by cytochalasin, but not colchicine. A novel 14-amino acid peptide agonist of the thrombin receptor fully mimics thrombin's morphoregulatory activity, indicating that thrombin-induced shape changes are receptor-mediated and not secondary to extracellular matrix degradation. Although thrombin receptors couple to phosphoinositide hydrolysis and Ca2+ mobilization, thrombin-induced shape changes appear to depend neither on the Ca2+/protein kinase C- nor the cyclic nucleotide-mediated signal transduction pathways; however, the morphological response to thrombin is blocked by pervanadate, an inhibitor of tyrosine phosphatases, and by broad-specificity kinase inhibitors. Our results suggest that the thrombin receptor communicates to an as-yet-uncharacterized effector to reorganize the actin cytoskeleton and to reverse the differentiated phenotype of neural cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alkaloids / pharmacology
  • Amino Acid Sequence
  • Animals
  • Calcium / metabolism
  • Cell Differentiation
  • Cell Line
  • Dose-Response Relationship, Drug
  • Genistein
  • Isoflavones / pharmacology
  • Kinetics
  • Mice
  • Molecular Sequence Data
  • Neurites / drug effects
  • Neurites / physiology*
  • Neurites / ultrastructure
  • Neuroblastoma
  • Neurons / cytology*
  • Neurons / drug effects
  • Oligopeptides / chemical synthesis
  • Oligopeptides / pharmacology*
  • Protein Kinase C / antagonists & inhibitors
  • Protein-Tyrosine Kinases / antagonists & inhibitors
  • Receptors, Cell Surface / drug effects
  • Receptors, Cell Surface / physiology*
  • Receptors, Thrombin
  • Second Messenger Systems*
  • Signal Transduction / drug effects
  • Staurosporine
  • Thrombin / metabolism
  • Thrombin / pharmacology*
  • Vanadates / pharmacology


  • Alkaloids
  • Isoflavones
  • Oligopeptides
  • Receptors, Cell Surface
  • Receptors, Thrombin
  • Vanadates
  • Genistein
  • Protein-Tyrosine Kinases
  • Protein Kinase C
  • Thrombin
  • Staurosporine
  • Calcium