Apoptotic pathway and MAPKs differentially regulate chemotropic responses of retinal growth cones

Douglas Simon Campbell, Christine E. Holt

Research output: Contribution to journalArticle

219 Citations (Scopus)

Abstract

Previous work has shown that guidance cues trigger rapid changes in protein dynamics in retinal growth cones: netrin-1 stimulates both protein synthesis and degradation, while Sema3A elicits synthesis, and LPA induces degradation. What signaling pathways are involved? Our studies confirm that p42/44 MAPK mediates netrin-1 responses and further show that inhibiting its activity blocks cue-induced protein synthesis. Unexpectedly, p38 MAPK is also activated by netrin-1 in retinal growth cones and is required for chemotropic responses and translation. Sema3A- and LPA-induced responses, by contrast, require a single MAPK, p42/p44 and p38, respectively. In addition, we report that caspase-3, an apoptotic protease, is rapidly activated by netrin-1 and LPA in a proteasome- and p38-dependent manner and is required for chemotropic responses. These findings suggest that the apoptotic pathway may be used locally to control protein levels in growth cones and that the differential activation of MAPK pathways may underlie cue-directed migration.

Original languageEnglish
Pages (from-to)939-952
Number of pages14
JournalNeuron
Volume37
Issue number6
DOIs
Publication statusPublished - 2003 Mar 27
Externally publishedYes

Fingerprint

Retinal Cone Photoreceptor Cells
Growth Cones
Semaphorin-3A
Cues
Mitogen-Activated Protein Kinase 1
p38 Mitogen-Activated Protein Kinases
Proteins
Mitogen-Activated Protein Kinase 3
Proteasome Endopeptidase Complex
Caspase 3
Proteolysis
Peptide Hydrolases
netrin-1

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Apoptotic pathway and MAPKs differentially regulate chemotropic responses of retinal growth cones. / Campbell, Douglas Simon; Holt, Christine E.

In: Neuron, Vol. 37, No. 6, 27.03.2003, p. 939-952.

Research output: Contribution to journalArticle

Campbell, Douglas Simon ; Holt, Christine E. / Apoptotic pathway and MAPKs differentially regulate chemotropic responses of retinal growth cones. In: Neuron. 2003 ; Vol. 37, No. 6. pp. 939-952.
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