MAP1B Regulates Axonal Development by Modulating Rho-GTPase Rac1 Activity

CAROLINA MONTENEGRO-VENEGAS, ELENA TORTOSA, SILVANA ROSSO, DIEGO PERETTI, FLAVIA BOLLATI, MARIANO BISBAL, IGNACIO JAUSORO, JESUS AVILA, ALFREDO CÁCERES, AND CHRISTIAN GONZALEZ-BILLAULT

MOLECULAR BIOLOGY OF THE CELL

AMER SOC CELL BIOLOGY

Año: 2010

1059-1524

Cultured neurons obtained from MAP1B-deficient mice have a delay in axon outgrowth and a reduced rate of axonal elongation as compared to neurons from wild-type mice. Here we show that MAP1B deficiency results in a significant decrease in Rac1 and cdc42 activity and a significant increase in Rho activity. We found that MAP1B interacted with Tiam1, a guanosine nucleotide exchange factor for Rac1. The decrease in Rac1/cdc42 activity was paralleled by decreases in the phosphorylation of the downstream effectors of these proteins, such as LIMK-1 and cofilin. The expression of a constitutively active form of Rac1, cdc42, or Tiam1 rescued the axon growth defect of MAP1B-deficient neurons. Taken together, these observations define a new and crucial function of MAP1B that we show to be required for efficient crosstalk between microtubules and the actin cytoskeleton during neuronal polarization.