MAP1B is required for Netrin 1 signaling in neuronal migration and axonal guidance.
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.
Del Río
José A
JA
Developmental Neurobiology and Regeneration Unit, Institut de Recerca Biomedica de Barcelona, Barcelona Science Park and Department of Cell Biology, University of Barcelona, Barcelona 08028, Spain.
González-Billault
Christian
C
Ureña
Jesús M
JM
Jiménez
Eva M
EM
Barallobre
María J
MJ
Pascual
Marta
M
Pujadas
Lluís
L
Simó
Sergi
S
La Torre
Anna
A
Wandosell
Francisco
F
Avila
Jesús
J
Soriano
Eduardo
E
D000818:Animals; D001369:Axons / Q000502:physiology*; D015153:Blotting, Western; D001921:Brain / Q000196:embryology / Q000378:metabolism*; D002460:Cell Line; D051360:Cyclin-Dependent Kinase 5; D018844:Cyclin-Dependent Kinases / Q000378:metabolism; D004591:Electrophoresis, Polyacrylamide Gel; D038362:Glycogen Synthase Kinase 3 / Q000378:metabolism; D006652:Histological Techniques; D007150:Immunohistochemistry; D051379:Mice; D008817:Mice, Mutant Strains; D008869:Microtubule-Associated Proteins / Q000378:metabolism* / Q000502:physiology; D009414:Nerve Growth Factors / Q000378:metabolism* / Q000502:physiology; D000075388:Netrin-1; D009474:Neurons / Q000502:physiology*; D010766:Phosphorylation; D015398:Signal Transduction / Q000502:physiology*; D025521:Tumor Suppressor Proteins
D008869:Microtubule-Associated Proteins; D009414:Nerve Growth Factors; C000617353:Ntn1 protein, mouse; D025521:Tumor Suppressor Proteins; C085284:microtubule-associated protein 1B; D000075388:Netrin-1; D051360:Cyclin-Dependent Kinase 5; C495906:Cdk5 protein, mouse; D018844:Cyclin-Dependent Kinases; D038362:Glycogen Synthase Kinase 3