title: A dynamic formin-dependent deep F-actin network in axons.
abstract: Although actin at neuronal growth cones is well-studied, much less is known about actin organization and dynamics along axon shafts and presynaptic boutons. Using probes that selectively label filamentous-actin (F-actin), we found focal "actin hotspots" along axons-spaced ∼3-4 µm apart-where actin undergoes continuous assembly/disassembly. These foci are a nidus for vigorous actin polymerization, generating long filaments spurting bidirectionally along axons-a phenomenon we call "actin trails." Super-resolution microscopy reveals intra-axonal deep actin filaments in addition to the subplasmalemmal "actin rings" described recently. F-actin hotspots colocalize with stationary axonal endosomes, and blocking vesicle transport diminishes the actin trails, suggesting mechanistic links between vesicles and F-actin kinetics. Actin trails are formin-but not Arp2/3-dependent and help enrich actin at presynaptic boutons. Finally, formin inhibition dramatically disrupts synaptic recycling. Collectively, available data suggest a two-tier F-actin organization in axons, with stable "actin rings" providing mechanical support to the plasma membrane and dynamic "actin trails" generating a flexible cytoskeletal network with putative physiological roles.
authors.affiliation: Department of Pathology, University of California, San Diego, La Jolla, CA 92093.
authors.forename: Archan
authors.initials: A
authors.lastname: Ganguly
authors.affiliation: Department of Pathology, University of California, San Diego, La Jolla, CA 92093.
authors.forename: Yong
authors.initials: Y
authors.lastname: Tang
authors.affiliation: Department of Pathology, University of California, San Diego, La Jolla, CA 92093.
authors.forename: Lina
authors.initials: L
authors.lastname: Wang
authors.affiliation: Department of Pathology, University of California, San Diego, La Jolla, CA 92093 Department of Neurosciences, University of California, San Diego, La Jolla, CA 92093.
authors.forename: Kelsey
authors.initials: K
authors.lastname: Ladt
authors.affiliation: Department of Pathology, University of California, San Diego, La Jolla, CA 92093.
authors.forename: Jonathan
authors.initials: J
authors.lastname: Loi
authors.affiliation: Aix Marseille Université, Centre National de la Recherche Scientifique, Centre de Recherche en Neurobiologie et Neurophysiologie de Marseille (CRN2M) UMR7286, 13344 Marseille, France.
authors.forename: Bénédicte
authors.initials: B
authors.lastname: Dargent
authors.affiliation: Aix Marseille Université, Centre National de la Recherche Scientifique, Centre de Recherche en Neurobiologie et Neurophysiologie de Marseille (CRN2M) UMR7286, 13344 Marseille, France.
authors.forename: Christophe
authors.initials: C
authors.lastname: Leterrier
authors.affiliation: Department of Pathology, University of California, San Diego, La Jolla, CA 92093 Department of Neurosciences, University of California, San Diego, La Jolla, CA 92093 s1roy@ucsd.edu.
authors.forename: Subhojit
authors.initials: S
authors.lastname: Roy
mesh_terms: D051376:Actin-Related Protein 2-3 Complex / Q000378:metabolism; D000199:Actins / Q000096:biosynthesis / Q000378:metabolism*; D000818:Animals; D001369:Axons / Q000378:metabolism*; D002462:Cell Membrane / Q000502:physiology; D005326:Fetal Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism*; D000080865:Formins; D049452:Green Fluorescent Proteins; D020439:Growth Cones / Q000378:metabolism*; D051379:Mice; D008840:Microfilament Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism*; D008870:Microtubules / Q000378:metabolism; D009687:Nuclear Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism*; D017729:Presynaptic Terminals / Q000378:metabolism; D013572:Synaptic Vesicles / Q000378:metabolism*
chemical_list: D051376:Actin-Related Protein 2-3 Complex; D000199:Actins; D005326:Fetal Proteins; D000080865:Formins; D008840:Microfilament Proteins; D009687:Nuclear Proteins; C485184:enhanced green fluorescent protein; D049452:Green Fluorescent Proteins