Clathrin packets move in slow axonal transport and deliver functional payloads to synapses.

Autor:	Ganguly A; Department of Pathology, University of California, San Diego, La Jolla, CA, USA., Sharma R; Department of Pathology, University of California, San Diego, La Jolla, CA, USA., Boyer NP; Department of Pathology, University of California, San Diego, La Jolla, CA, USA., Wernert F; Aix Marseille Université, CNRS, INP UMR7051, NeuroCyto, Marseille, France., Phan S; Department of Neurosciences, University of California, San Diego, La Jolla, CA, USA; National Center for Microscopy and Imaging Research, University of California, San Diego, La Jolla, CA, USA., Boassa D; Department of Neurosciences, University of California, San Diego, La Jolla, CA, USA; National Center for Microscopy and Imaging Research, University of California, San Diego, La Jolla, CA, USA., Parra L; Department of Pathology, University of California, San Diego, La Jolla, CA, USA., Das U; Department of Pathology, University of California, San Diego, La Jolla, CA, USA; Department of Neurosciences, University of California, San Diego, La Jolla, CA, USA., Caillol G; Aix Marseille Université, CNRS, INP UMR7051, NeuroCyto, Marseille, France., Han X; Department of Cell Biology, The Scripps Research Institute, La Jolla, CA, USA., Yates JR 3rd; Department of Cell Biology, The Scripps Research Institute, La Jolla, CA, USA., Ellisman MH; Department of Neurosciences, University of California, San Diego, La Jolla, CA, USA; National Center for Microscopy and Imaging Research, University of California, San Diego, La Jolla, CA, USA., Leterrier C; Aix Marseille Université, CNRS, INP UMR7051, NeuroCyto, Marseille, France., Roy S; Department of Pathology, University of California, San Diego, La Jolla, CA, USA; Department of Neurosciences, University of California, San Diego, La Jolla, CA, USA. Electronic address: sroy@ucsd.edu.
Jazyk:	angličtina
Zdroj:	Neuron [Neuron] 2021 Sep 15; Vol. 109 (18), pp. 2884-2901.e7.
DOI:	10.1016/j.neuron.2021.08.016
Abstrakt:	In non-neuronal cells, clathrin has established roles in endocytosis, with clathrin cages enclosing plasma membrane infoldings, followed by rapid disassembly and reuse of monomers. However, in neurons, clathrin is conveyed in slow axonal transport over days to weeks, and the underlying transport/targeting mechanisms, mobile cargo structures, and even its precise presynaptic localization and physiologic role are unclear. Combining live imaging, photobleaching/conversion, mass spectrometry, electron microscopy, and super-resolution imaging, we found that unlike in dendrites, where clathrin cages rapidly assemble and disassemble, in axons, clathrin and related proteins organize into stable "transport packets" that are unrelated to endocytosis and move intermittently on microtubules, generating an overall slow anterograde flow. At synapses, multiple clathrin packets abut synaptic vesicle (SV) clusters, and clathrin packets also exchange between synaptic boutons in a microtubule-dependent "superpool." Within synaptic boundaries, clathrin is surprisingly dynamic, continuously exchanging between local clathrin assemblies, and its depletion impairs SV recycling. Our data provide a conceptual framework for understanding clathrin trafficking and presynaptic targeting that has functional implications. Competing Interests: Declaration of interests The authors declare no competing interests. (Copyright © 2021 Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
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