title: Nanoparticle-assisted optical tethering of endosomes reveals the cooperative function of dyneins in retrograde axonal transport.
abstract: Dynein-dependent transport of organelles from the axon terminals to the cell bodies is essential to the survival and function of neurons. However, quantitative knowledge of dyneins on axonal organelles and their collective function during this long-distance transport is lacking because current technologies to do such measurements are not applicable to neurons. Here, we report a new method termed nanoparticle-assisted optical tethering of endosomes (NOTE) that made it possible to study the cooperative mechanics of dyneins on retrograde axonal endosomes in live neurons. In this method, the opposing force from an elastic tether causes the endosomes to gradually stall under load and detach with a recoil velocity proportional to the dynein forces. These recoil velocities reveal that the axonal endosomes, despite their small size, can recruit up to 7 dyneins that function as independent mechanical units stochastically sharing load, which is vital for robust retrograde axonal transport. This study shows that NOTE, which relies on controlled generation of reactive oxygen species, is a viable method to manipulate small cellular cargos that are beyond the reach of current technology.
authors.affiliation: Department of Chemistry, Stanford University, 380 Roth Way, Stanford, CA 94305, USA.
authors.forename: Praveen D
authors.initials: PD
authors.lastname: Chowdary
authors.affiliation: Department of Chemistry, Stanford University, 380 Roth Way, Stanford, CA 94305, USA.
authors.forename: Daphne L
authors.initials: DL
authors.lastname: Che
authors.affiliation: Department of Chemistry, Stanford University, 380 Roth Way, Stanford, CA 94305, USA.
authors.forename: Luke
authors.initials: L
authors.lastname: Kaplan
authors.affiliation: Department of Chemistry, Massachussets Institute of Technology, 77 Massachussets Ave, Cambridge, MA 02139, USA.
authors.forename: Ou
authors.initials: O
authors.lastname: Chen
authors.affiliation: School of Chemical and Biomedical Engineering, Nanyang Technological University, 62 Nanyang Drive, N1.3, B2-05, Singapore 637459.
authors.forename: Kanyi
authors.initials: K
authors.lastname: Pu
authors.affiliation: Department of Chemistry, Massachussets Institute of Technology, 77 Massachussets Ave, Cambridge, MA 02139, USA.
authors.forename: Moungi
authors.initials: M
authors.lastname: Bawendi
authors.affiliation: Department of Chemistry, Stanford University, 380 Roth Way, Stanford, CA 94305, USA.
authors.forename: Bianxiao
authors.initials: B
authors.lastname: Cui
mesh_terms: D001370:Axonal Transport / Q000502:physiology*; D001369:Axons / Q000378:metabolism* / Q000502:physiology*; D002478:Cells, Cultured; D004398:Dyneins / Q000378:metabolism*; D011992:Endosomes / Q000378:metabolism* / Q000502:physiology*; D053758:Nanoparticles / Q000008:administration & dosage*; D009474:Neurons / Q000378:metabolism / Q000502:physiology
chemical_list: D004398:Dyneins