title: Hierarchical microtubule organization controls axon caliber and transport and determines synaptic structure and stability.
abstract: The dimensions of axons and synaptic terminals determine cell-intrinsic properties of neurons; however, the cellular mechanisms selectively controlling establishment and maintenance of neuronal compartments remain poorly understood. Here, we show that two giant Drosophila Ankyrin2 isoforms, Ank2-L and Ank2-XL, and the MAP1B homolog Futsch form a membrane-associated microtubule-organizing complex that determines axonal diameter, supports axonal transport, and provides independent control of synaptic dimensions and stability. Ank2-L controls microtubule and synaptic stability upstream of Ank2-XL that selectively controls microtubule organization. Synergistically with Futsch, Ank2-XL provides three-dimensional microtubule organization and is required to establish appropriate synaptic dimensions and release properties. In axons, the Ank2-XL/Futsch complex establishes evenly spaced, grid-like microtubule organization and determines axonal diameter in the absence of neurofilaments. Reduced microtubule spacing limits anterograde transport velocities of mitochondria and synaptic vesicles. Our data identify control of microtubule architecture as a central mechanism to selectively control neuronal dimensions, functional properties, and connectivity.
authors: Friedrich Miescher Institute for Biomedical Research, Maulbeerstrasse 66, 4058 Basel, Switzerland.
authors: Raiko
authors: R
authors: Stephan
authors: Heinrich-Heine-University Düsseldorf, Universitätsstrasse 1, 40225 Düsseldorf, Germany.
authors: Bernd
authors: B
authors: Goellner
authors: Friedrich Miescher Institute for Biomedical Research, Maulbeerstrasse 66, 4058 Basel, Switzerland.
authors: Eliza
authors: E
authors: Moreno
authors: Department of Anatomy and Cell Biology, University of Iowa, 51 Newton Road, Iowa City, IA 52242, USA.
authors: C Andrew
authors: CA
authors: Frank
authors: Friedrich Miescher Institute for Biomedical Research, Maulbeerstrasse 66, 4058 Basel, Switzerland.
authors: Tabea
authors: T
authors: Hugenschmidt
authors: Friedrich Miescher Institute for Biomedical Research, Maulbeerstrasse 66, 4058 Basel, Switzerland.
authors: Christel
authors: C
authors: Genoud
authors: Heinrich-Heine-University Düsseldorf, Universitätsstrasse 1, 40225 Düsseldorf, Germany.
authors: Hermann
authors: H
authors: Aberle
authors: Friedrich Miescher Institute for Biomedical Research, Maulbeerstrasse 66, 4058 Basel, Switzerland. Electronic address: jan.pielage@fmi.ch.
authors: Jan
authors: J
authors: Pielage
mesh_terms: D000818:Animals; D030801:Animals, Genetically Modified / Q000235:genetics / Q000378:metabolism*; D017487:Ankyrins / Q000378:metabolism*; D001370:Axonal Transport / Q000502:physiology*; D003599:Cytoskeleton / Q000378:metabolism; D029721:Drosophila Proteins / Q000378:metabolism*; D004331:Drosophila melanogaster / Q000235:genetics / Q000378:metabolism*; D004594:Electrophysiology; D007091:Image Processing, Computer-Assisted; D007124:Immunoenzyme Techniques; D008869:Microtubule-Associated Proteins / Q000378:metabolism*; D008870:Microtubules / Q000378:metabolism*; D009469:Neuromuscular Junction / Q000378:metabolism; D009474:Neurons / Q000166:cytology / Q000378:metabolism; D013569:Synapses / Q000502:physiology*
chemical_list: C498993:Ank2 protein, Drosophila; D017487:Ankyrins; D029721:Drosophila Proteins; D008869:Microtubule-Associated Proteins; C409635:futsch protein, Drosophila; C085284:microtubule-associated protein 1B