RRC ID 54993
Author 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 JC, Andrieux A, Hazan J.
Title Motor axon navigation relies on Fidgetin-like 1-driven microtubule plus end dynamics.
Journal 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.
Volume 217(5)
Pages 1719-1738
Published 2018-5-7
DOI 10.1083/jcb.201604108
PII jcb.201604108
PMID 29535193
PMC PMC5940295
MeSH Adenosine Triphosphatases / chemistry Adenosine Triphosphatases / metabolism* Animals Axon Guidance* Axons / metabolism* Cytoskeleton / metabolism Gene Knockdown Techniques Growth Cones / metabolism Humans Larva / metabolism Locomotion Microtubule-Associated Proteins / metabolism Microtubules / metabolism* Motor Neurons / metabolism Nuclear Proteins / chemistry Nuclear Proteins / metabolism* Polymerization Protein Isoforms / metabolism Spinal Cord / metabolism
IF 8.891
Times Cited 3
Zebrafish Tg(CM-isl1:GFP)