title: MAP1B regulates microtubule dynamics by sequestering EB1/3 in the cytosol of developing neuronal cells.
abstract: MAP1B, a structural microtubule (MT)-associated protein highly expressed in developing neurons, plays a key role in neurite and axon extension. However, not all molecular mechanisms by which MAP1B controls MT dynamics during these processes have been revealed. Here, we show that MAP1B interacts directly with EB1 and EB3 (EBs), two core 'microtubule plus-end tracking proteins' (+TIPs), and sequesters them in the cytosol of developing neuronal cells. MAP1B overexpression reduces EBs binding to plus-ends, whereas MAP1B downregulation increases binding of EBs to MTs. These alterations in EBs behaviour lead to changes in MT dynamics, in particular overstabilization and looping, in growth cones of MAP1B-deficient neurons. This contributes to growth cone remodelling and a delay in axon outgrowth. Together, our findings define a new and crucial role of MAP1B as a direct regulator of EBs function and MT dynamics during neurite and axon extension. Our data provide a new layer of MT regulation: a classical MAP, which binds to the MT lattice and not to the end, controls effective concentration of core +TIPs thereby regulating MTs at their plus-ends.
authors.affiliation: Centro de Biología Molecular Severo Ochoa (CSIC-UAM), Department of Molecular Neurobiology, Madrid, Spain.
authors.forename: Elena
authors.initials: E
authors.lastname: Tortosa
authors.forename: Niels
authors.initials: N
authors.lastname: Galjart
authors.forename: Jesús
authors.initials: J
authors.lastname: Avila
authors.forename: Carmen Laura
authors.initials: CL
authors.lastname: Sayas
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D003600:Cytosol / Q000378:metabolism*; D057809:HEK293 Cells; D006801:Humans; D007700:Kinetics; D051379:Mice; D018345:Mice, Knockout; D008869:Microtubule-Associated Proteins / Q000235:genetics / Q000378:metabolism*; D008870:Microtubules / Q000378:metabolism*; D008954:Models, Biological; D055495:Neurogenesis / Q000235:genetics / Q000502:physiology; D009474:Neurons / Q000378:metabolism* / Q000502:physiology / Q000648:ultrastructure; D011485:Protein Binding / Q000502:physiology; D055503:Protein Multimerization / Q000235:genetics; D021381:Protein Transport / Q000235:genetics
chemical_list: C405804:EB1 microtubule binding proteins; C522423:EB3 protein, mouse; D008869:Microtubule-Associated Proteins; C085284:microtubule-associated protein 1B