title: Periodic actin structures in neuronal axons are required to maintain microtubules.
abstract: Axons are cable-like neuronal processes wiring the nervous system. They contain parallel bundles of microtubules as structural backbones, surrounded by regularly spaced actin rings termed the periodic membrane skeleton (PMS). Despite being an evolutionarily conserved, ubiquitous, highly ordered feature of axons, the function of PMS is unknown. Here we studied PMS abundance, organization, and function, combining versatile Drosophila genetics with superresolution microscopy and various functional readouts. Analyses with 11 actin regulators and three actin-targeting drugs suggest that PMS contains short actin filaments that are depolymerization resistant and sensitive to spectrin, adducin, and nucleator deficiency, consistent with microscopy-derived models proposing PMS as specialized cortical actin. Upon actin removal, we observed gaps in microtubule bundles, reduced microtubule polymerization, and reduced axon numbers, suggesting a role of PMS in microtubule organization. These effects become strongly enhanced when carried out in neurons lacking the microtubule-stabilizing protein Short stop (Shot). Combining the aforementioned actin manipulations with Shot deficiency revealed a close correlation between PMS abundance and microtubule regulation, consistent with a model in which PMS-dependent microtubule polymerization contributes to their maintenance in axons. We discuss potential implications of this novel PMS function along axon shafts for axon maintenance and regeneration.
authors.affiliation: Faculty of Biology, Medicine and Health, University of Manchester, Manchester M13 9PT, United Kingdom.
authors.forename: Yue
authors.initials: Y
authors.lastname: Qu
authors.affiliation: Faculty of Biology, Medicine and Health, University of Manchester, Manchester M13 9PT, United Kingdom.
authors.forename: Ines
authors.initials: I
authors.lastname: Hahn
authors.affiliation: Rutherford Appleton Laboratory, Science and Technology Facilities Council, Didcot OX11 0QX, United Kingdom.
authors.forename: Stephen E D
authors.initials: SE
authors.lastname: Webb
authors.affiliation: Faculty of Biology, Medicine and Health, University of Manchester, Manchester M13 9PT, United Kingdom.|School of Mathematics, University of Manchester, Manchester M13 9PL, United Kingdom.
authors.forename: Simon P
authors.initials: SP
authors.lastname: Pearce
authors.affiliation: Faculty of Biology, Medicine and Health, University of Manchester, Manchester M13 9PT, United Kingdom Andreas.Prokop@manchester.ac.uk.
authors.forename: Andreas
authors.initials: A
authors.lastname: Prokop
mesh_terms: D008841:Actin Cytoskeleton / Q000378:metabolism; D000199:Actins / Q000378:metabolism* / Q000502:physiology; D000818:Animals; D001369:Axons / Q000378:metabolism / Q000502:physiology*; D002478:Cells, Cultured; D003599:Cytoskeleton / Q000378:metabolism; D004330:Drosophila / Q000378:metabolism; D029721:Drosophila Proteins / Q000378:metabolism; D008840:Microfilament Proteins / Q000378:metabolism; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D008870:Microtubules / Q000378:metabolism / Q000502:physiology*; D009474:Neurons / Q000378:metabolism; D014404:Tubulin / Q000378:metabolism
chemical_list: D000199:Actins; D029721:Drosophila Proteins; D008840:Microfilament Proteins; D008869:Microtubule-Associated Proteins; D014404:Tubulin