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J Cell Biol. 2019 Oct 7;218(10):3290-3306. doi: 10.1083/jcb.201805128. Epub 2019 Sep 19.

FIGNL1 associates with KIF1Bβ and BICD1 to restrict dynein transport velocity during axon navigation.

Author information

1
Sorbonne Université, University Pierre and Marie Curie-Université Paris 6, Institut de Biologie Paris Seine, Unité de Neuroscience Paris Seine, Centre National de la Recherche Scientifique, Unité Mixte Recherche 8246, Institut National de la Santé et de la Recherche Médicale U1130, Paris, France.
2
Department of Genetics and Developmental Biology, Institut Curie, Paris, France.
3
Sorbonne Université, University Pierre and Marie Curie-Université Paris 6, Institut de Biologie Paris Seine, Unité de Neuroscience Paris Seine, Centre National de la Recherche Scientifique, Unité Mixte Recherche 8246, Institut National de la Santé et de la Recherche Médicale U1130, Paris, France jamile.hazan@upmc.fr.
4
Sorbonne Université, University Pierre and Marie Curie-Université Paris 6, Institut de Biologie Paris Seine, Unité de Neuroscience Paris Seine, Centre National de la Recherche Scientifique, Unité Mixte Recherche 8246, Institut National de la Santé et de la Recherche Médicale U1130, Paris, France coralie.fassier@upmc.fr.

Abstract

Neuronal connectivity relies on molecular motor-based axonal transport of diverse cargoes. Yet the precise players and regulatory mechanisms orchestrating such trafficking events remain largely unknown. We here report the ATPase Fignl1 as a novel regulator of bidirectional transport during axon navigation. Using a yeast two-hybrid screen and coimmunoprecipitation assays, we showed that Fignl1 binds the kinesin Kif1bβ and the dynein/dynactin adaptor Bicaudal D-1 (Bicd1) in a molecular complex including the dynactin subunit dynactin 1. Fignl1 colocalized with Kif1bβ and showed bidirectional mobility in zebrafish axons. Notably, Kif1bβ and Fignl1 loss of function similarly altered zebrafish motor axon pathfinding and increased dynein-based transport velocity of Rab3 vesicles in these navigating axons, pinpointing Fignl1/Kif1bβ as a dynein speed limiter complex. Accordingly, disrupting dynein/dynactin activity or Bicd1/Fignl1 interaction induced motor axon pathfinding defects characteristic of Fignl1 gain or loss of function, respectively. Finally, pharmacological inhibition of dynein activity partially rescued the axon pathfinding defects of Fignl1-depleted larvae. Together, our results identify Fignl1 as a key dynein regulator required for motor circuit wiring.

PMID:
31541015
PMCID:
PMC6781435
[Available on 2020-04-07]
DOI:
10.1083/jcb.201805128

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