Role of heterotrimeric G-proteins in lysophosphatidic acid-mediated neurite retraction by RhoA-dependent and -independent mechanisms in N1E-115 cells.
Cell Signal
; 18(5): 715-28, 2006 May.
Article
em En
| MEDLINE
| ID: mdl-16122906
ABSTRACT
In neuronal cells, current evidence suggests that G(13)alpha and RhoA play significant roles in LPA-mediated neurite retraction; however, the contribution of other G-proteins to this process is less well-understood. We provide evidence that LPA activation of G(13), G(q) and G(i) occurs rapidly in neuroblastoma cells, but that stimulation of RhoA is transient whereas the activation of G(q)- and G(i)-mediated pathways is sustained. In addition to G(13)alpha, we demonstrate that G(q)alpha is capable of promoting neurite retraction. G(q)-mediated retraction is RhoA-independent and is likely mediated via a mechanism involving protein kinase C and calcium flux. Additionally, we provide evidence that activation of adenylyl cyclase via G(s) inhibits RhoA-mediated neurite retraction via protein kinase A-mediated inhibition of RhoA action. Taken together, we hypothesize that LPA promotes neurite retraction via RhoA-dependent and -independent pathways involving G(13) and G(q), respectively, and that agonists that activate G(s) inhibit the RhoA-dependent pathway.
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Base de dados:
MEDLINE
Assunto principal:
Lisofosfolipídeos
/
Neuritos
/
Isoformas de Proteínas
/
Proteínas Heterotriméricas de Ligação ao GTP
/
Proteína rhoA de Ligação ao GTP
Limite:
Animals
Idioma:
En
Ano de publicação:
2006
Tipo de documento:
Article