title: Microtubule minus-end binding protein CAMSAP2 controls axon specification and dendrite development.
abstract: In neurons, most microtubules are not associated with a central microtubule-organizing center (MTOC), and therefore, both the minus and plus-ends of these non-centrosomal microtubules are found throughout the cell. Microtubule plus-ends are well established as dynamic regulatory sites in numerous processes, but the role of microtubule minus-ends has remained poorly understood. Using live-cell imaging, high-resolution microscopy, and laser-based microsurgery techniques, we show that the CAMSAP/Nezha/Patronin family protein CAMSAP2 specifically localizes to non-centrosomal microtubule minus-ends and is required for proper microtubule organization in neurons. CAMSAP2 stabilizes non-centrosomal microtubules and is required for neuronal polarity, axon specification, and dendritic branch formation in vitro and in vivo. Furthermore, we found that non-centrosomal microtubules in dendrites are largely generated by γ-Tubulin-dependent nucleation. We propose a two-step model in which γ-Tubulin initiates the formation of non-centrosomal microtubules and CAMSAP2 stabilizes the free microtubule minus-ends in order to control neuronal polarity and development.
authors.affiliation: Cell Biology, Faculty of Science, Utrecht University, 3584 CH, Utrecht, The Netherlands; Department of Neuroscience, Erasmus Medical Center, 3015 GE Rotterdam, The Netherlands.
authors.forename: Kah Wai
authors.initials: KW
authors.lastname: Yau
authors.affiliation: Cell Biology, Faculty of Science, Utrecht University, 3584 CH, Utrecht, The Netherlands.
authors.forename: Sam F B
authors.initials: SF
authors.lastname: van Beuningen
authors.affiliation: Cell Biology, Faculty of Science, Utrecht University, 3584 CH, Utrecht, The Netherlands.
authors.forename: Inês
authors.initials: I
authors.lastname: Cunha-Ferreira
authors.affiliation: Cell Biology, Faculty of Science, Utrecht University, 3584 CH, Utrecht, The Netherlands.
authors.forename: Bas M C
authors.initials: BM
authors.lastname: Cloin
authors.affiliation: Department of Translational Neuroscience, Brain Center Rudolf Magnus, University Medical Center Utrecht, 3584 CG, Utrecht, The Netherlands.
authors.forename: Eljo Y
authors.initials: EY
authors.lastname: van Battum
authors.affiliation: Cell Biology, Faculty of Science, Utrecht University, 3584 CH, Utrecht, The Netherlands.
authors.forename: Lena
authors.initials: L
authors.lastname: Will
authors.affiliation: Cell Biology, Faculty of Science, Utrecht University, 3584 CH, Utrecht, The Netherlands.
authors.forename: Philipp
authors.initials: P
authors.lastname: Schätzle
authors.affiliation: Cell Biology, Faculty of Science, Utrecht University, 3584 CH, Utrecht, The Netherlands.
authors.forename: Roderick P
authors.initials: RP
authors.lastname: Tas
authors.affiliation: Cell Biology, Faculty of Science, Utrecht University, 3584 CH, Utrecht, The Netherlands.
authors.forename: Jaap
authors.initials: J
authors.lastname: van Krugten
authors.affiliation: Cell Biology, Faculty of Science, Utrecht University, 3584 CH, Utrecht, The Netherlands.
authors.forename: Eugene A
authors.initials: EA
authors.lastname: Katrukha
authors.affiliation: Cell Biology, Faculty of Science, Utrecht University, 3584 CH, Utrecht, The Netherlands.
authors.forename: Kai
authors.initials: K
authors.lastname: Jiang
authors.affiliation: Cell Biology, Faculty of Science, Utrecht University, 3584 CH, Utrecht, The Netherlands.
authors.forename: Phebe S
authors.initials: PS
authors.lastname: Wulf
authors.affiliation: Cell Biology, Faculty of Science, Utrecht University, 3584 CH, Utrecht, The Netherlands.
authors.forename: Marina
authors.initials: M
authors.lastname: Mikhaylova
authors.affiliation: Cell Biology, Faculty of Science, Utrecht University, 3584 CH, Utrecht, The Netherlands.
authors.forename: Martin
authors.initials: M
authors.lastname: Harterink
authors.affiliation: Department of Translational Neuroscience, Brain Center Rudolf Magnus, University Medical Center Utrecht, 3584 CG, Utrecht, The Netherlands.
authors.forename: R Jeroen
authors.initials: RJ
authors.lastname: Pasterkamp
authors.affiliation: Cell Biology, Faculty of Science, Utrecht University, 3584 CH, Utrecht, The Netherlands.
authors.forename: Anna
authors.initials: A
authors.lastname: Akhmanova
authors.affiliation: Cell Biology, Faculty of Science, Utrecht University, 3584 CH, Utrecht, The Netherlands. Electronic address: l.kapitein@uu.nl.
authors.forename: Lukas C
authors.initials: LC
authors.lastname: Kapitein
authors.affiliation: Cell Biology, Faculty of Science, Utrecht University, 3584 CH, Utrecht, The Netherlands; Department of Neuroscience, Erasmus Medical Center, 3015 GE Rotterdam, The Netherlands. Electronic address: c.hoogenraad@uu.nl.
authors.forename: Casper C
authors.initials: CC
authors.lastname: Hoogenraad
mesh_terms: D000818:Animals; D001369:Axons / Q000378:metabolism* / Q000648:ultrastructure; D003598:Cytoskeletal Proteins / Q000378:metabolism*; D003712:Dendrites / Q000378:metabolism* / Q000648:ultrastructure; D006624:Hippocampus / Q000196:embryology / Q000378:metabolism / Q000648:ultrastructure; D006801:Humans; D008869:Microtubule-Associated Proteins; D008870:Microtubules / Q000378:metabolism* / Q000648:ultrastructure; D017966:Pyramidal Cells / Q000378:metabolism* / Q000648:ultrastructure; D051381:Rats
chemical_list: C573192:CAMSAP2 protein, human; D003598:Cytoskeletal Proteins; D008869:Microtubule-Associated Proteins