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Exosomes surf on filopodia to enter cells at endocytic hot spots, and shuttle with endosomes to scan the endoplasmic reticulum – a highway to the cell.

Heusermann, Wolf and Hean, Justin and Trojer, Dominic and Von Bueren, Stefan and Graff-Meyer, Alexandra and Genoud, Christel and Martin, Katrin and Voshol, Johannes and Morrissey, David and ElAndaloussi, Samir and Wood, Matthew and Meisner Kober, Nicole-Claudia (2016) Exosomes surf on filopodia to enter cells at endocytic hot spots, and shuttle with endosomes to scan the endoplasmic reticulum – a highway to the cell. Journal of Cell Biology, 213 (2). pp. 173-184. ISSN DOI: 10.1083

Abstract

Exosomes are nanovesicles released by virtually all cells which act as intercellular messengers by transfer of protein, lipid and RNA cargo. Their quantitative efficiency, routes of cell uptake and subcellular fate within recipient cells remain elusive. We quantitatively characterize exosome cell uptake which saturates with dose and time and reaches near 100 % ‘transduction’ efficiency at picomolar concentrations. Highly reminiscent of pathogenic bacteria and viruses, exosomes are recruited as single vesicles to the cell body by surfing on filopodia, as well as filopodia grabbing and pulling motions to reach endocytic hot spots at the filopodial base. Following internalization, exosomes shuttle with endocytic vesicles to scan the endoplasmic reticulum before being sorted into the lysosome as their final intracellular destination. Our data quantify and explain the efficiency of exosome internalization by recipient cells, establish a new parallel between exosome and virus host cell interaction and suggest unanticipated routes of subcellular cargo delivery.

vonBueren S1, Graff-Meyer A4, Genoud C4, Martin K5, Voshol H1, Morrissey DV6, 7, EL Andaloussi S3,8,
Wood MJ3, Meisner-Kober NC1

Item Type: Article
Keywords: exosomes, drug delivery, extracellular vesicles
Date Deposited: 13 Sep 2018 00:45
Last Modified: 13 Sep 2018 00:45
URI: https://oak.novartis.com/id/eprint/26374

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