Inhibitors of protein kinases abolish ECM-mediated promotion of neuronal polarity

André Lochter, Melitta Schachner

Research output: Contribution to journalArticlepeer-review

10 Scopus citations

Abstract

Different extracellular matrix (ECM) molecules, when presented to hippocampal neurons in culture in a substrate-bound form, exert strikingly similar effects on the establishment of neuronal polarity, i.e., the growth of axon-like major neurites is favored, whereas extension of dendrite-like minor neurites is inhibited. To gain insight into the underlying signal transduction processes, we have investigated the effects of modulators of protein kinase activity on the morphology of neurons cultured on tenascin-R, tenascin-C, and laminin-entactin substrates. We found differential effects of broad-spectrum protein kinase inhibitors: H-7 promoted the growth of minor neurites, whereas H-8 reduced the growth of major neurites on ECM but not control substrates. In contrast, chelerythrine, a specific inhibitor of protein kinase C, selectively affected growth of both minor and major neurites on control, but not on ECM substrates. Finally, reagents which elevate intracellular cAMP levels facilitated growth of minor neurites and inhibited growth of major neurites and thus interfered with the establishment of a polarized phenotype on both ECM and control substrates. Our results suggest that protein kinases mediate the effects of ECM molecules on neuronal polarity and that different kinases control extension of axons and dendrites.

Original languageEnglish (US)
Pages (from-to)124-129
Number of pages6
JournalExperimental cell research
Volume235
Issue number1
DOIs
StatePublished - Aug 25 1997
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Cell Biology

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