Thrombin receptor activation causes rapid neural cell rounding and neurite retraction independent of classic second messengers.
Open Access
- 15 July 1992
- journal article
- Published by Rockefeller University Press in The Journal of cell biology
- Vol. 118 (2), 411-419
- https://doi.org/10.1083/jcb.118.2.411
Abstract
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.Keywords
This publication has 52 references indexed in Scilit:
- Molecular cloning of a functional thrombin receptor reveals a novel proteolytic mechanism of receptor activationCell, 1991
- A common denominator of growth cone guidance and collapse?Trends in Neurosciences, 1990
- Thrombin and its inhibitors regulate morphological and biochemical differentiation of astrocytes in vitroDevelopmental Brain Research, 1990
- Neurite guidance moleculesCurrent Opinion in Cell Biology, 1989
- Evidence that calcium may control neurite outgrowth by regulating the stability of actin filaments.The Journal of cell biology, 1989
- Thrombin Interactions with Central Nervous System Tissue and Implications of These InteractionsaAnnals of the New York Academy of Sciences, 1986
- Phorbol ester and diacylglycerol mimic growth factors in raising cytoplasmic pHNature, 1984
- Rapid rounding of human epidermoid carcinoma cells A-431 induced by epidermal growth factorThe Journal of cell biology, 1981
- Serum triggers a sequence of rapid ionic conductance changes in quiescent neuroblastoma cellsNature, 1979
- Cell surface action of thrombin is sufficient to initiate division of chick cellsCell, 1978