MAP1B is required for netrin 1 signaling in neuronal migration and axonal guidance

José A. Del Río, Christian González-Billault, Jesús M. Ureña, Eva M. Jiménez, María J. Barallobre, Marta Pascual, Lluís Pujadas, Sergi Simo Olivar, Anna La Torre Vila, Francisco Wandosell, Jesús Ávila, Eduardo Soriano

Research output: Contribution to journalArticle

100 Scopus citations

Abstract

Background: The signaling cascades governing neuronal migration and axonal guidance link extracellular signals to cytoskeletal components. MAP1B is a neuron-specific microtubule-associated protein implicated in the crosstalk between microtubules and actin filaments. Results: Here we show that Netrin 1 regulates, both in vivo and in vitro, mode I MAP1B phosphorylation, which controls MAP1B activity, in a signaling pathway that depends essentially on the kinases GSK3 and CDK5. We also show that map1B-deficient neurons from the lower rhombic lip and other brain regions have reduced chemoattractive responses to Netrin 1 in vitro. Furthermore, map1B mutant mice have severe abnormalities, similar to those described in netrin 1-deficient mice, in axonal tracts and in the pontine nuclei. Conclusions: These data indicate that MAP1B phosphorylation is controlled by Netrin 1 and that the lack of MAP1B impairs Netrin 1-mediated chemoattraction in vitro and in vivo. Thus, MAP1B may be a downstream effector in the Netrin 1-signaling pathway.

Original languageEnglish (US)
Pages (from-to)840-850
Number of pages11
JournalCurrent Biology
Volume14
Issue number10
DOIs
StatePublished - May 25 2004
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)

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    Del Río, J. A., González-Billault, C., Ureña, J. M., Jiménez, E. M., Barallobre, M. J., Pascual, M., Pujadas, L., Simo Olivar, S., La Torre Vila, A., Wandosell, F., Ávila, J., & Soriano, E. (2004). MAP1B is required for netrin 1 signaling in neuronal migration and axonal guidance. Current Biology, 14(10), 840-850. https://doi.org/10.1016/j.cub.2004.04.046