MAP1B enhances microtubule assembly rates and axon extension rates in developing neurons.
The microtubule-associated protein MAP1B is known to have important roles in neuronal development, particularly during neuronal migration and axonogenesis, but its precise molecular actions are unknown. We used RNA interference silencing of protein expression to specifically knock down MAP1B in cultured embryonic rat cortical neurons. Reduction of MAP1B in these neurons is associated with several abnormal morphological phenotypes including the production of more highly branched and slower growing axons than normal. MAP1B binds to dynamic microtubules and indirect evidence suggests that MAP1B regulates microtubule dynamics. We used the +TIP protein EB3 to assess the dynamic behaviour and orientation of microtubules in neurons in which MAP1B had been knocked down. This revealed a reduction in the speed of microtubule growth in the proximal and distal axon shaft, but not in growth cone filopodia. These observations suggest that the function of MAP1B is to suppress axon branching and enhance axon growth and that this is achieved by maintaining dynamic microtubule growth. To test this hypothesis we expressed MAP1B in a cell line that does not have endogenous MAP1B, this led to an increase in microtubule elongation rates. These findings show that MAP1B enhances microtubule assembly rates and axon extension rates in developing neurons by binding to dynamic microtubules.
The MRC Centre for Developmental Neurobiology, New Hunt's House, Guy's Campus, King's College London, London SE1 1UL, United Kingdom.
Stephen R
SR
Tymanskyj
Timothy M E
TM
Scales
Phillip R
PR
Gordon-Weeks
D000818:Animals; D001369:Axons / Q000378:metabolism* / Q000502:physiology; D019556:COS Cells; D002460:Cell Line; D002478:Cells, Cultured; D002522:Chlorocebus aethiops; D055785:Gene Knockdown Techniques; D020439:Growth Cones / Q000378:metabolism; D008869:Microtubule-Associated Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D008870:Microtubules / Q000378:metabolism* / Q000502:physiology; D009474:Neurons / Q000166:cytology* / Q000378:metabolism / Q000502:physiology*; D011554:Pseudopodia / Q000378:metabolism; D051381:Rats; D014162:Transfection
D008869:Microtubule-Associated Proteins; C085284:microtubule-associated protein 1B