Monoclonal antibody 8A2-induced retraction appears to be mediated by protein phosphorylation in goldfish retinal ganglion cell axons

Sarah G. Finnegan, Vance Lemmon, Edward Koenig

Research output: Contribution to journalArticle

10 Citations (Scopus)

Abstract

We have recently demonstrated that binding by monoclonal antibody (mAb) 8A2 to regenerating retinal ganglion cell axons in goldfish explants specifically induces a sustained, actin-based retraction response that is similar in most respects to a spontaneous retraction (S.G. Finnegan, V. Lemmon, and E. Koenig, Cell Motil. Cytoskeleton, 1992). Experiments were conducted to evaluate potential signal transduction pathways that may play a role in mediating retraction, using the mAb 8A2 retraction model system. Potential roles of cAMP, elevated intracellular calcium, or calmodulin-dependent processes were probed and the results did not appear to implicate them in either the induction or the maintenance of the axon retraction response. In contrast, treatment with phorbol 12-myristate 13-acetate, but not with inactive phorbol esters, induced a retraction response, although the response was more variable and less robust than that produced by mAb 8A2. However, both forms of induction were blocked by staurosporine, a nonspecific kinase inhibitor. Okadaic acid, a potent serine/threonine phosphatase inhibitor produced a very robust retraction response, and subthreshold doses significantly potentiated the retraction response induced by mAb 8A2. Genistein inhibited the mAb 8A2-induced retraction response at concentrations selective for tyrosine kinase activity in a dose-dependent manner. These findings are consistent with the hypothesis that an augmented phosphorylation state of one or more axonal proteins, perhaps catalyzed in part by protein kinase C, produces a sustained physiological retraction. In addition, tyrosine kinase may be involved in transducing surface-mediated interactions that trigger retraction, including the binding reaction signal of mAb 8A2.

Original languageEnglish
Pages (from-to)230-242
Number of pages13
JournalDevelopmental Biology
Volume156
Issue number1
StatePublished - Dec 1 1993
Externally publishedYes

Fingerprint

Goldfish
Retinal Ganglion Cells
Axons
Monoclonal Antibodies
Phosphorylation
Proteins
Protein-Tyrosine Kinases
Okadaic Acid
Staurosporine
Genistein
Phosphoprotein Phosphatases
Phorbol Esters
Calmodulin
Cytoskeleton
Protein Kinase C
Actins
Signal Transduction
Acetates
Phosphotransferases
Maintenance

ASJC Scopus subject areas

  • Developmental Biology

Cite this

Monoclonal antibody 8A2-induced retraction appears to be mediated by protein phosphorylation in goldfish retinal ganglion cell axons. / Finnegan, Sarah G.; Lemmon, Vance; Koenig, Edward.

In: Developmental Biology, Vol. 156, No. 1, 01.12.1993, p. 230-242.

Research output: Contribution to journalArticle

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