title: Local synthesis of dynein cofactors matches retrograde transport to acutely changing demands.
abstract: Cytoplasmic dynein mediates retrograde transport in axons, but it is unknown how its transport characteristics are regulated to meet acutely changing demands. We find that stimulus-induced retrograde transport of different cargos requires the local synthesis of different dynein cofactors. Nerve growth factor (NGF)-induced transport of large vesicles requires local synthesis of Lis1, while smaller signalling endosomes require both Lis1 and p150Glued. Lis1 synthesis is also triggered by NGF withdrawal and required for the transport of a death signal. Association of Lis1 transcripts with the microtubule plus-end tracking protein APC is required for their translation in response to NGF stimulation but not for their axonal recruitment and translation upon NGF withdrawal. These studies reveal a critical role for local synthesis of dynein cofactors for the transport of specific cargos and identify association with RNA-binding proteins as a mechanism to establish functionally distinct pools of a single transcript species in axons.
authors.affiliation: Medical Scientist Training Program, College of Physicians and Surgeons, Columbia University, New York, New York 10032, USA.
authors.forename: Joseph M
authors.initials: JM
authors.lastname: Villarin
authors.affiliation: Integrated Program in Cellular, Molecular and Biomedical Studies, College of Physicians and Surgeons, Columbia University, New York, New York 10032, USA.
authors.forename: Ethan P
authors.initials: EP
authors.lastname: McCurdy
authors.affiliation: Medical Scientist Training Program, College of Physicians and Surgeons, Columbia University, New York, New York 10032, USA.
authors.forename: José C
authors.initials: JC
authors.lastname: Martínez
authors.affiliation: The Taub Institute for Research on Alzheimer's Disease and the Aging Brain, College of Physicians and Surgeons, Columbia University, New York, New York 10032, USA.|Department of Pathology and Cell Biology, College of Physicians and Surgeons, Columbia University, New York, New York 10032, USA.
authors.forename: Ulrich
authors.identifier: http://orcid.org/0000-0002-8061-2861
authors.initials: U
authors.lastname: Hengst
mesh_terms: D000818:Animals; D001370:Axonal Transport / Q000187:drug effects; D001483:Base Sequence; D002478:Cells, Cultured; D000072159:Dynactin Complex / Q000235:genetics / Q000378:metabolism*; D004398:Dyneins / Q000378:metabolism*; D005260:Female; D005727:Ganglia, Spinal / Q000166:cytology / Q000196:embryology; D015870:Gene Expression / Q000187:drug effects; D008297:Male; D020932:Nerve Growth Factor / Q000494:pharmacology; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D009474:Neurons / Q000378:metabolism*; D034622:RNA Interference; D017207:Rats, Sprague-Dawley
chemical_list: D000072159:Dynactin Complex; D009419:Nerve Tissue Proteins; C516550:Pafah1b1 protein, rat; D020932:Nerve Growth Factor; D004398:Dyneins