Lysophosphatidic acid-induced neurite retraction in PC12 cells

Control by phosphoinositide-Ca 2+ signaling and Rho

Gabor Tigyi, David J. Fischer, Ágnes Sebök, Charles Yang, David L. Dyer, Ricardo Miledi

Research output: Contribution to journalArticle

176 Citations (Scopus)

Abstract

The endogenous phospholipid mediator lysophosphatidic acid (LPA) caused growth cone collapse, neurite retraction, and cell flattening in differentiated PC12 cells. Neurite retraction was blocked by cytochalasin B and ADP-ribosylation of the small-molecular-weight G protein Rho by the Clostridium botulinum C-3 toxin. LPA induced a transient rise in the level of inositol 1,4,5-trisphosphate, and retraction was blocked by inhibitors of phospholipase â. Repeated application of LPA elicited homologous desensitization of the Ca 2+ mobilization response. The activation of the phosphoinositide (PIP)-Ca 2+ second messenger system played a permissive role in the morphoregulatory response. Blockers of protein kinase C - chelerythrine, a myristoylated pseudo-substrate peptide, staurosporine, and depletion of protein kinase C from the cells by long-term phorbol ester treatment - all diminshed neurite retraction by interfering with LPA-induced Ca 2+ mobilization, which was required for the withdrawal of neurites. A brief 15-min treatment with 4β-phorbol 12-myristate 13-acetate also blocked retraction and Ca 2+ mobilization, by inactivating the LPA receptor. Inhibition of protein tyrosine phosphorylation by herbimycin diminished retraction. Although activation of the PIP-Ca 2+ second messenger system appears necessary for the Rho-mediated rearrangements of the actin cytoskeleton, bradykinin, which activates similar signaling events, failed to cause retraction, indicating that a yet unidentified novel mechanism is also involved in the LPA-induced morphoregulatory response.

Original languageEnglish (US)
Pages (from-to)537-548
Number of pages12
JournalJournal of Neurochemistry
Volume66
Issue number2
StatePublished - Feb 1 1996

Fingerprint

PC12 Cells
Neurites
Phosphatidylinositols
Second Messenger Systems
Protein Kinase C
Chemical activation
Lysophosphatidic Acid Receptors
Clostridium
Growth Cones
rho GTP-Binding Proteins
Phosphorylation
Cytochalasin B
Inositol 1,4,5-Trisphosphate
Staurosporine
Phospholipases
Bradykinin
Phorbol Esters
Actin Cytoskeleton
Adenosine Diphosphate
Tyrosine

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Cellular and Molecular Neuroscience

Cite this

Lysophosphatidic acid-induced neurite retraction in PC12 cells : Control by phosphoinositide-Ca 2+ signaling and Rho. / Tigyi, Gabor; Fischer, David J.; Sebök, Ágnes; Yang, Charles; Dyer, David L.; Miledi, Ricardo.

In: Journal of Neurochemistry, Vol. 66, No. 2, 01.02.1996, p. 537-548.

Research output: Contribution to journalArticle

Tigyi, Gabor ; Fischer, David J. ; Sebök, Ágnes ; Yang, Charles ; Dyer, David L. ; Miledi, Ricardo. / Lysophosphatidic acid-induced neurite retraction in PC12 cells : Control by phosphoinositide-Ca 2+ signaling and Rho. In: Journal of Neurochemistry. 1996 ; Vol. 66, No. 2. pp. 537-548.
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