TY - JOUR
T1 - MAP1B is required for netrin 1 signaling in neuronal migration and axonal guidance
AU - Del Río, José A.
AU - González-Billault, Christian
AU - Ureña, Jesús M.
AU - Jiménez, Eva M.
AU - Barallobre, María J.
AU - Pascual, Marta
AU - Pujadas, Lluís
AU - Simo Olivar, Sergi
AU - La Torre Vila, Anna
AU - Wandosell, Francisco
AU - Ávila, Jesús
AU - Soriano, Eduardo
PY - 2004/5/25
Y1 - 2004/5/25
N2 - 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.
AB - 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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U2 - 10.1016/j.cub.2004.04.046
DO - 10.1016/j.cub.2004.04.046
M3 - Article
C2 - 15186740
AN - SCOPUS:3042602928
VL - 14
SP - 840
EP - 850
JO - Current Biology
JF - Current Biology
SN - 0960-9822
IS - 10
ER -