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

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.

journal_name

Exp Cell Res

authors

Lochter A,Schachner M

doi

10.1006/excr.1997.3655

subject

Has Abstract

pub_date

1997-08-25 00:00:00

pages

124-9

issue

1

eissn

0014-4827

issn

1090-2422

pii

S0014-4827(97)93655-7

journal_volume

235

pub_type

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