Lysophosphatidic acid-induced neurite retraction in PC12 cells: neurite-protective effects of cyclic AMP signaling
- PMID: 8592124
- DOI: 10.1046/j.1471-4159.1996.66020549.x
Lysophosphatidic acid-induced neurite retraction in PC12 cells: neurite-protective effects of cyclic AMP signaling
Abstract
Effects of the cyclic AMP second messenger system were studied on the retraction of neurites elicited by the phospholipid mediator lysophosphatidic acid (LPA) in PC12 cells. LPA stimulation inhibited adenylyl cyclase, indicating that the LPA receptor couples to the heterotrimeric Gi proteins. However, pertussis toxin or expression of dominant negative Ras did not prevent neurite retraction. In contrast, cholera toxin, forskolin, and application of dibutyryl-cyclic AMP prevented neurite retraction. The neurite-protective effect of forskolin was blocked by Rp-adenosine 3',5'-phosphorothioate. Forskolin and dibutyryl-cyclic AMP both failed to protect neurites in A126-1B2 and 123.7 cells, which lack cyclic AMP-activated protein kinase. Data indicate that elevation of cyclic AMP levels triggers a cyclic AMP-activated protein kinase-dependent mechanism that opposes the functioning of the morphoregulatory signaling activated by LPA. ADP-ribosylation of Rho by the Clostridium botulinum C-3 toxin in 123.7 cells caused neuronal differentiation, indicated by neurite extension, and blocked LPA-induced neurite retraction. LPA activates Gq- and Gi-linked signaling in parallel; therefore, a morphoregulatory signaling network hypothesis is proposed versus the simplistic approach of a signaling pathway. The signaling network integrates the receptor-activated individual, sequential, and parallel signaling events into an interactive network whose individual components may fulfill required and permissive functions encoding the cellular response.
Similar articles
-
Lysophosphatidic acid-induced neurite retraction in PC12 cells: control by phosphoinositide-Ca2+ signaling and Rho.J Neurochem. 1996 Feb;66(2):537-48. doi: 10.1046/j.1471-4159.1996.66020537.x. J Neurochem. 1996. PMID: 8592123
-
Inhibition of lysophosphatidate- and thrombin-induced neurite retraction and neuronal cell rounding by ADP ribosylation of the small GTP-binding protein Rho.J Cell Biol. 1994 Aug;126(3):801-10. doi: 10.1083/jcb.126.3.801. J Cell Biol. 1994. PMID: 8045941 Free PMC article.
-
Lysophosphatidic acid induces neurite retraction in differentiated neuroblastoma cells via GSK-3β activation.Mol Cells. 2011 May;31(5):483-9. doi: 10.1007/s10059-011-1036-0. Epub 2011 Apr 14. Mol Cells. 2011. PMID: 21499833 Free PMC article.
-
Regulation of neuronal cytoskeleton by lysophosphatidic acid: role of GSK-3.Biochim Biophys Acta. 2002 May 23;1582(1-3):144-53. doi: 10.1016/s1388-1981(02)00149-x. Biochim Biophys Acta. 2002. PMID: 12069822 Review.
-
Intercellular signaling by lysophosphatidate.Cell Adhes Commun. 1998 Mar;5(3):221-35. doi: 10.3109/15419069809040293. Cell Adhes Commun. 1998. PMID: 9686319 Review.
Cited by
-
Lysophosphatidylinositol Induced Morphological Changes and Stress Fiber Formation through the GPR55-RhoA-ROCK Pathway.Int J Mol Sci. 2022 Sep 18;23(18):10932. doi: 10.3390/ijms231810932. Int J Mol Sci. 2022. PMID: 36142844 Free PMC article.
-
Lysophosphatidic Acid Signalling in Nervous System Development and Function.Neuromolecular Med. 2021 Mar;23(1):68-85. doi: 10.1007/s12017-020-08630-2. Epub 2020 Nov 5. Neuromolecular Med. 2021. PMID: 33151452 Review.
-
LPA1 , LPA2 , LPA4 , and LPA6 receptor expression during mouse brain development.Dev Dyn. 2019 May;248(5):375-395. doi: 10.1002/dvdy.23. Epub 2019 Mar 27. Dev Dyn. 2019. PMID: 30847983 Free PMC article.
-
Lysophosphatidic acid receptor type 2 activation contributes to secondary damage after spinal cord injury in mice.Brain Behav Immun. 2019 Feb;76:258-267. doi: 10.1016/j.bbi.2018.12.007. Epub 2018 Dec 11. Brain Behav Immun. 2019. PMID: 30550929 Free PMC article.
-
'Crystal' Clear? Lysophospholipid Receptor Structure Insights and Controversies.Trends Pharmacol Sci. 2018 Nov;39(11):953-966. doi: 10.1016/j.tips.2018.08.006. Trends Pharmacol Sci. 2018. PMID: 30343728 Free PMC article. Review.
Publication types
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Other Literature Sources
Miscellaneous