MAP1B regulates axonal development by modulating Rho-GTPase Rac1 activity.
Cultured neurons obtained from MAP1B-deficient mice have a delay in axon outgrowth and a reduced rate of axonal elongation compared with 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 cross-talk between microtubules and the actin cytoskeleton during neuronal polarization.
Montenegro-Venegas
Carolina
C
Department of Biology, Universidad de Chile, Santiago, Chile.
Tortosa
Elena
E
Rosso
Silvana
S
Peretti
Diego
D
Bollati
Flavia
F
Bisbal
Mariano
M
Jausoro
Ignacio
I
Avila
Jesus
J
Cáceres
Alfredo
A
Gonzalez-Billault
Christian
C
D051339:Actin Depolymerizing Factors / Q000378:metabolism; D000199:Actins / Q000378:metabolism; D000818:Animals; D001369:Axons / Q000187:drug effects / Q000201:enzymology* / Q000378:metabolism; D015638:Cytochalasin D / Q000494:pharmacology; D003599:Cytoskeleton / Q000187:drug effects / Q000378:metabolism; D020662:Guanine Nucleotide Exchange Factors / Q000378:metabolism; D007700:Kinetics; D054461:Lim Kinases / Q000378:metabolism; D051379:Mice; D008869:Microtubule-Associated Proteins / Q000172:deficiency / Q000378:metabolism*; D008954:Models, Biological; D010766:Phosphorylation / Q000187:drug effects; D011485:Protein Binding / Q000187:drug effects; D000075684:T-Lymphoma Invasion and Metastasis-inducing Protein 1; D020764:cdc42 GTP-Binding Protein / Q000378:metabolism; D020830:rac1 GTP-Binding Protein / Q000378:metabolism*; D020742:rhoA GTP-Binding Protein / Q000378:metabolism
D051339:Actin Depolymerizing Factors; D000199:Actins; D020662:Guanine Nucleotide Exchange Factors; D008869:Microtubule-Associated Proteins; D000075684:T-Lymphoma Invasion and Metastasis-inducing Protein 1; C513260:Tiam1 protein, mouse; C085284:microtubule-associated protein 1B; D015638:Cytochalasin D; D054461:Lim Kinases; C515893:Limk1 protein, mouse; D020764:cdc42 GTP-Binding Protein; D020830:rac1 GTP-Binding Protein; D020742:rhoA GTP-Binding Protein