title: Bidirectional actin transport is influenced by microtubule and actin stability.
abstract: Local and long-distance transport of cytoskeletal proteins is vital to neuronal maintenance and growth. Though recent progress has provided insight into the movement of microtubules and neurofilaments, mechanisms underlying the movement of actin remain elusive, in large part due to rapid transitions between its filament states and its diverse cellular localization and function. In this work, we integrated live imaging of rat sensory neurons, image processing, multiple regression analysis, and mathematical modeling to perform the first quantitative, high-resolution investigation of GFP-actin identity and movement in individual axons. Our data revealed that filamentous actin densities arise along the length of the axon and move short but significant distances bidirectionally, with a net anterograde bias. We directly tested the role of actin and microtubules in this movement. We also confirmed a role for actin densities in extension of axonal filopodia, and demonstrated intermittent correlation of actin and mitochondrial movement. Our results support a novel mechanism underlying slow component axonal transport, in which the stability of both microtubule and actin cytoskeletal components influence the mobility of filamentous actin.
authors.affiliation: Fischell Department of Bioengineering, University of Maryland, College Park, MD, USA.
authors.forename: Joshua
authors.initials: J
authors.lastname: Chetta
authors.affiliation: Fischell Department of Bioengineering, University of Maryland, College Park, MD, USA.
authors.forename: James M
authors.initials: JM
authors.lastname: Love
authors.affiliation: Department of Bioengineering, University of California, San Diego, La Jolla, CA, USA.
authors.forename: Brian G
authors.initials: BG
authors.lastname: Bober
authors.affiliation: Fischell Department of Bioengineering, University of Maryland, College Park, MD, USA. sbshah@ucsd.edu.|Departments of Orthopaedic Surgery and Bioengineering, University of California, San Diego, 9500 Gilman Drive, MC 0863, La Jolla, CA, 92093, USA. sbshah@ucsd.edu.
authors.forename: Sameer B
authors.initials: SB
authors.lastname: Shah
mesh_terms: D000199:Actins / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D001370:Axonal Transport / Q000502:physiology; D002478:Cells, Cultured; D003599:Cytoskeleton / Q000378:metabolism; D047630:Depsipeptides / Q000494:pharmacology; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D008870:Microtubules / Q000187:drug effects / Q000378:metabolism*; D008928:Mitochondria / Q000378:metabolism; D008962:Models, Theoretical; D009474:Neurons / Q000166:cytology / Q000378:metabolism; D015739:Nocodazole / Q000494:pharmacology; D021381:Protein Transport; D011554:Pseudopodia / Q000378:metabolism; D051381:Rats; D012044:Regression Analysis
chemical_list: D000199:Actins; D047630:Depsipeptides; C057531:jasplakinolide; D049452:Green Fluorescent Proteins; D015739:Nocodazole
keywords: Actin; Axonal transport; Cytoskeleton; Microtubule; Slow component B