[HTML][HTML] MAP1B is required for Netrin 1 signaling in neuronal migration and axonal guidance

JA Del Rı́o, C González-Billault, JM Ureña… - Current Biology, 2004 - cell.com
JA Del Rı́o, C González-Billault, JM Ureña, EM Jiménez, MJ Barallobre, M Pascual…
Current Biology, 2004cell.com
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 …
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.
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