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J Cell Biol. 2018 May 7;217(5):1719-1738. doi: 10.1083/jcb.201604108. Epub 2018 Mar 13.

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

Author information

1
Sorbonne Universités, Université Pierre et Marie Curie-Université Paris 6, Institut de Biologie Paris-Seine, Unité de Neuroscience Paris Seine, Centre National de la Recherche Scientifique UMR 8246, Institut National de la Santé et de la Recherche Médicale U1130, Paris, France coralie.fassier@upmc.fr.
2
Sorbonne Universités, Université Pierre et Marie Curie-Université Paris 6, Institut de Biologie Paris-Seine, Unité de Neuroscience Paris Seine, Centre National de la Recherche Scientifique UMR 8246, Institut National de la Santé et de la Recherche Médicale U1130, Paris, France.
3
Institut National de la Santé et de la Recherche Médicale U1216, Université Grenoble Alpes, Grenoble Institut Neurosciences, Grenoble, France.
4
Centre for Interdisciplinary Research in Biology, Collège de France, Paris, France.
5
Department of Genetics and Developmental Biology, Institut Curie, Paris, France.
6
Sorbonne Universités, Université Pierre et Marie Curie-Université Paris 6, Institut de Biologie Paris-Seine, Centre National de la Recherche Scientifique FR3631, Paris, France.
7
Sorbonne Universités, Université Pierre et Marie Curie-Université Paris 6, Institut de Biologie Paris-Seine, Biologie du Développement, Centre National de la Recherche Scientifique UMR7622, Paris, France.
8
Medical Research Council Centre for Developmental Neurobiology, King's College London, Guy's Hospital Campus, London, England, UK.

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.

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