title: Stage-Dependent Axon Transport of Proteasomes Contributes to Axon Development.
abstract: Axon extension at the growing tip requires elevated local protein supply, with a capability sustainable over long axons in varying environments. The exact mechanisms, however, remain elusive. Here we report that axon-promoting factors elicited a retrograde transport-dependent removal of proteasomes from nascent axon terminals, thereby increasing protein stability at axon tips. Such an effect occurred through phosphorylation of a dynein-interacting proteasome adaptor protein Ecm29. During the transition from immature neurites to nascent axons in cultured hippocampal neurons, live-cell imaging revealed a significant increase of the retrograde axonal transport of fluorescently labeled 20S proteasomes. This retrograde proteasome transport depended on neuron stage and increased with axon lengths. Blockade of retrograde transport caused accumulation of proteasomes, reduction of axon growth, and attenuation of growth-associated Par6 at the axon tip of newly polarized neurons. Our results delineate a regulatory mechanism that controls proteasome abundance via preferential transport required for axon development in newborn neurons.
authors.affiliation: Institute of Molecular Biology, Academia Sinica, 128 Academia Road, Section 2, Nankang, Taipei 11529, Taiwan.
authors.forename: Meng-Tsung
authors.initials: MT
authors.lastname: Hsu
authors.affiliation: Institute of Physics, Academia Sinica, 128 Academia Road, Section 2, Nankang, Taipei 11529, Taiwan.
authors.forename: Chin-Lin
authors.initials: CL
authors.lastname: Guo
authors.affiliation: Institute of Molecular Biology, Academia Sinica, 128 Academia Road, Section 2, Nankang, Taipei 11529, Taiwan.
authors.forename: Angela Y
authors.initials: AY
authors.lastname: Liou
authors.affiliation: Institute of Molecular Biology, Academia Sinica, 128 Academia Road, Section 2, Nankang, Taipei 11529, Taiwan.
authors.forename: Ting-Ya
authors.initials: TY
authors.lastname: Chang
authors.affiliation: Institute of Molecular Biology, Academia Sinica, 128 Academia Road, Section 2, Nankang, Taipei 11529, Taiwan.
authors.forename: Ming-Chong
authors.initials: MC
authors.lastname: Ng
authors.affiliation: Leiden Institute of Chemistry, Leiden University, Rapenburg 70, 2311 EZ Leiden, the Netherlands.
authors.forename: Bogdan I
authors.initials: BI
authors.lastname: Florea
authors.affiliation: Leiden Institute of Chemistry, Leiden University, Rapenburg 70, 2311 EZ Leiden, the Netherlands.
authors.forename: Herman S
authors.initials: HS
authors.lastname: Overkleeft
authors.affiliation: Institute of Molecular Biology, Academia Sinica, 128 Academia Road, Section 2, Nankang, Taipei 11529, Taiwan.
authors.forename: Yen-Lin
authors.initials: YL
authors.lastname: Wu
authors.affiliation: Institute of Atomic and Molecular Sciences, Academia Sinica, 128 Academia Road, Section 2, Nankang, Taipei 11529, Taiwan.
authors.forename: Jung-Chi
authors.initials: JC
authors.lastname: Liao
authors.affiliation: Institute of Molecular Biology, Academia Sinica, 128 Academia Road, Section 2, Nankang, Taipei 11529, Taiwan. Electronic address: plcheng@imb.sinica.edu.tw.
authors.forename: Pei-Lin
authors.initials: PL
authors.lastname: Cheng
mesh_terms: D000818:Animals; D001370:Axonal Transport / Q000502:physiology*; D001369:Axons / Q000502:physiology*; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism; D002478:Cells, Cultured; D000242:Cyclic AMP / Q000494:pharmacology; D004398:Dyneins / Q000378:metabolism; D004622:Embryo, Mammalian / Q000166:cytology / Q000378:metabolism; D006624:Hippocampus / Q000166:cytology* / Q000378:metabolism; D015151:Immunoblotting; D016501:Neurites / Q000502:physiology*; D009474:Neurons / Q000166:cytology* / Q000378:metabolism; D010766:Phosphorylation; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism*; D051381:Rats
chemical_list: D019208:Brain-Derived Neurotrophic Factor; D000242:Cyclic AMP; D046988:Proteasome Endopeptidase Complex; D004398:Dyneins