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Exosomes surf on filopodia to enter cells at endocytic hot spots and shuttle within endosomes to scan the ER

Heusermann, Wolf and Hean, Justin and Trojer, Dominic and Steib, Emmanuelle and Von Bueren, Stefan and Graff-Meyer, Alexandra and Genoud, Christel and Martin, Katrin and Pizzato, Nicolas 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 within endosomes to scan the ER. Journal of Cell Biology, 213 (2). pp. 173-184. ISSN 1540-8140

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 within 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.

Item Type: Article
Keywords: exosomes
Date Deposited: 12 Aug 2016 00:45
Last Modified: 12 Aug 2016 00:45
URI: https://oak.novartis.com/id/eprint/28867

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