Lysophosphatidic acid-induced neurite retraction in PC12 cells

Neurite-protective effects of cyclic AMP signaling

Gabor Tigyi, David J. Fischer, Ágnes Sebök, Frakeetta Marshall, David L. Dyer, Ricardo Miledi

Research output: Contribution to journalArticle

120 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)549-558
Number of pages10
JournalJournal of Neurochemistry
Volume66
Issue number2
StatePublished - Feb 1 1996

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PC12 Cells
Neurites
Cyclic AMP
Colforsin
Bucladesine
AMP-Activated Protein Kinases
Lysophosphatidic Acid Receptors
Clostridium
Cholera Toxin
Pertussis Toxin
Second Messenger Systems
Adenylyl Cyclases
Adenosine
Adenosine Diphosphate
lysophosphatidic acid
Phospholipids
Proteins

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Cellular and Molecular Neuroscience

Cite this

Tigyi, G., Fischer, D. J., Sebök, Á., Marshall, F., Dyer, D. L., & Miledi, R. (1996). Lysophosphatidic acid-induced neurite retraction in PC12 cells: Neurite-protective effects of cyclic AMP signaling. Journal of Neurochemistry, 66(2), 549-558.

Lysophosphatidic acid-induced neurite retraction in PC12 cells : Neurite-protective effects of cyclic AMP signaling. / Tigyi, Gabor; Fischer, David J.; Sebök, Ágnes; Marshall, Frakeetta; Dyer, David L.; Miledi, Ricardo.

In: Journal of Neurochemistry, Vol. 66, No. 2, 01.02.1996, p. 549-558.

Research output: Contribution to journalArticle

Tigyi, G, Fischer, DJ, Sebök, Á, Marshall, F, Dyer, DL & Miledi, R 1996, 'Lysophosphatidic acid-induced neurite retraction in PC12 cells: Neurite-protective effects of cyclic AMP signaling', Journal of Neurochemistry, vol. 66, no. 2, pp. 549-558.
Tigyi, Gabor ; Fischer, David J. ; Sebök, Ágnes ; Marshall, Frakeetta ; Dyer, David L. ; Miledi, Ricardo. / Lysophosphatidic acid-induced neurite retraction in PC12 cells : Neurite-protective effects of cyclic AMP signaling. In: Journal of Neurochemistry. 1996 ; Vol. 66, No. 2. pp. 549-558.
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