Inhibition of lysophosphatidate- and thrombin-induced neurite retraction and neuronal cell rounding by ADP ribosylation of the small GTP-binding protein Rho
| Autor: | E J van Corven, N Morii, Kees Jalink, S Narumiya, Wouter H. Moolenaar, Trudi Hengeveld |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 1994 |
| Předmět: |
RHOA
Botulinum Toxins Neurite Ribose Molecular Sequence Data Cell Line Proto-Oncogene Proteins p21(ras) chemistry.chemical_compound Mice GTP-Binding Proteins Lysophosphatidic acid Neurites Animals Amino Acid Sequence Growth cone Cytoskeleton Actin ADP Ribose Transferases Neurons biology Thrombin Cell Biology Articles Molecular biology Actins Cell biology Adenosine Diphosphate chemistry Cell culture Second messenger system biology.protein Lysophospholipids rhoA GTP-Binding Protein Muscle Contraction |
| Zdroj: | The Journal of Cell Biology |
| ISSN: | 1540-8140 0021-9525 |
| Popis: | Addition of the bioactive phospholipid lysophosphatidic acid (LPA) or a thrombin receptor-activating peptide (TRP) to serum-starved N1E-115 or NG108-15 neuronal cells causes rapid growth cone collapse, neurite retraction, and transient rounding of the cell body. These shape changes appear to be driven by receptor-mediated contraction of the cortical actomyosin system independent of classic second messengers. Treatment of the cells with Clostridium botulinum C3 exoenzyme, which ADP-ribosylates and thereby inactivates the Rho small GTP-binding protein, inhibits LPA- and TRP-induced force generation and subsequent shape changes. C3 also inhibits LPA-induced neurite retraction in PC12 cells. Biochemical analysis reveals that the ADP-ribosylated substrate is RhoA. Prolonged C3 treatment of cells maintained in 10% serum induces the phenotype of serum-starved cells, with initial cell flattening being followed by neurite outgrowth; such C3-differentiated cells fail to retract their neurites in response to agonists. We conclude that RhoA is essential for receptor-mediated force generation and ensuing neurite retraction in N1E-115 and PC12 cells, and that inactivation of RhoA by ADP-ribosylation abolishes actomyosin contractility and promotes neurite outgrowth. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|