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PMID: 9634563 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

cAMP-mediated regulation of neurotrophin-induced collapse of nerve growth cones.

The Journal of neuroscience : the official journal of the Society for Neuroscience ·Vol. 18 ·No. 13 ·1998-07-01 ·Pages 4973-84

Wang Q, Zheng JQ

Abstract

Neurotrophins are known to promote the survival, differentiation, and neurite outgrowth of developing neurons. Here we report that acutely applied brain-derived neurotrophic factor (BDNF) induces rapid growth cone collapse and neurite retraction of embryonic Xenopus spinal neurons in culture. The collapsing effect of BDNF depends on the activation of Trk receptor tyrosine kinase, requires an influx of extracellular Ca2+, and is regulated by cAMP-dependent activity. Elevation of intracellular cAMP levels ([cAMP]i) by forskolin or (Sp)-cAMP completely blocked the collapsing effect, whereas inhibition of protein kinase A (PKA) by (Rp)-cAMP potentiated the collapsing action. BDNF-induced growth cone collapse was only observed in 6 hr cultures but not in 24 hr cultures. However, inhibition of PKA by (Rp)-cAMP restored the collapsing response of these "old" neurons in 24 hr cultures, suggesting that embryonic Xenopus spinal neurons may upregulate their endogenous cAMP-dependent activity during development in culture, leading to the blockade of their collapsing response to BDNF. Taken together, our results suggest the presence of cross-talk between Ca2+- and cAMP-signaling pathways involved in the collapsing action of neurotrophins, in which the cAMP-pathway regulates the Ca2+-mediated signal transduction required for BDNF-induced collapse. By modulating the cAMP-dependent activity through the intrinsic programming or interaction with other factors present in the environment, a neuron thus could respond to the same extracellular factors with different morphological and cellular changes at different stages during development.

MeSH Terms
Actins/physiology Animals Brain-Derived Neurotrophic Factor/pharmacology Calcium/metabolism Cell Size/drug effects,physiology Cells, Cultured Cyclic AMP/metabolism Cytoskeleton/chemistry,physiology Cytosol/metabolism Nerve Growth Factors/pharmacology Neurites/chemistry,drug effects,metabolism Neurons/cytology,metabolism,ultrastructure Proto-Oncogene Proteins/metabolism Receptor Protein-Tyrosine Kinases/metabolism Receptor, Ciliary Neurotrophic Factor Receptor, trkA Receptors, Nerve Growth Factor/metabolism Spinal Cord/cytology Xenopus
Chemicals
Actins Brain-Derived Neurotrophic Factor Nerve Growth Factors Proto-Oncogene Proteins Receptor, Ciliary Neurotrophic Factor Receptors, Nerve Growth Factor Cyclic AMP Receptor Protein-Tyrosine Kinases Receptor, trkA Calcium
Authors & Affiliations
2 authors, click to expand affiliations / ORCID
Wang Q
Department of Neuroscience and Cell Biology, University of Medicine and Dentistry of New Jersey, Robert Wood Johnson Medical School, Piscataway, New Jersey 08854, USA.
Zheng J Q
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Article Info
Journal
The Journal of neuroscience : the official journal of the Society for Neuroscience
Abbr.
J Neurosci
ISSN
0270-6474
Published
1998-07-01
Pages
4973-84
Language
English
Region
United States
NLM ID
8102140
PMCID
PMC6792562
Subset
IM
External Links
PubMed source PMC Full Text View journal details
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