PUBLICATION

Motor axon navigation relies on Fidgetin-like 1-driven microtubule plus end dynamics

Authors
Fassier, C., Fréal, A., Gasmi, L., Delphin, C., Ten Martin, D., De Gois, S., Tambalo, M., Bosc, C., Mailly, P., Revenu, C., Peris, L., Bolte, S., Schneider-Maunoury, S., Houart, C., Nothias, F., Larcher, J.C., Andrieux, A., Hazan, J.
ID
ZDB-PUB-180315-3
Date
2018
Source
The Journal of cell biology   217(5): 1719-1738 (Journal)
Registered Authors
Hazan, Jamile, Houart, Corinne, Revenu, Celine, Schneider-Maunoury, Sylvie
Keywords
none
MeSH Terms
  • Locomotion
  • Motor Neurons/metabolism
  • Axon Guidance*
  • Animals
  • Microtubule-Associated Proteins/metabolism
  • Adenosine Triphosphatases/chemistry
  • Adenosine Triphosphatases/metabolism*
  • Microtubules/metabolism*
  • Spinal Cord/metabolism
  • Cytoskeleton/metabolism
  • Nuclear Proteins/chemistry
  • Nuclear Proteins/metabolism*
  • Growth Cones/metabolism
  • Protein Isoforms/metabolism
  • Polymerization
  • Axons/metabolism*
  • Larva/metabolism
  • Humans
  • Gene Knockdown Techniques
(all 19)
PubMed
29535193 Full text @ J. Cell Biol.
Abstract
During neural circuit assembly, extrinsic signals are integrated into changes in growth cone (GC) cytoskeleton underlying axon guidance decisions. Microtubules (MTs) were shown to play an instructive role in GC steering. However, the numerous actors required for MT remodeling during axon navigation and their precise mode of action are far from being deciphered. Using loss- and gain-of-function analyses during zebrafish development, we identify in this study the meiotic clade adenosine triphosphatase Fidgetin-like 1 (Fignl1) as a key GC-enriched MT-interacting protein in motor circuit wiring and larval locomotion. We show that Fignl1 controls GC morphology and behavior at intermediate targets by regulating MT plus end dynamics and growth directionality. We further reveal that alternative translation of Fignl1 transcript is a sophisticated mechanism modulating MT dynamics: a full-length isoform regulates MT plus end-tracking protein binding at plus ends, whereas shorter isoforms promote their depolymerization beneath the cell cortex. Our study thus pinpoints Fignl1 as a multifaceted key player in MT remodeling underlying motor circuit connectivity.
Genes / Markers
Figures
Figure Gallery (13 images) / 2
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Expression
Phenotype
Mutations / Transgenics
Allele Construct Type Affected Genomic Region
ku20TgTransgenic Insertion
    ml2TgTransgenic Insertion
      rw0TgTransgenic Insertion
        rw021TgTransgenic Insertion
          zf519TgTransgenic Insertion
            zf532TgTransgenic Insertion
              1 - 6 of 6
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              Human Disease / Model
              No data available
              Sequence Targeting Reagents
              Target Reagent Reagent Type
              fignl1MO1-fignl1MRPHLNO
              fignl1MO2-fignl1MRPHLNO
              1 - 2 of 2
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              Fish
              Antibodies
              Orthology
              No data available
              Engineered Foreign Genes
              Marker Marker Type Name
              EGFPEFGEGFP
              GAL4EFGGAL4
              GFPEFGGFP
              1 - 3 of 3
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              Mapping
              No data available