Exosomes surf on filopodia to enter cells at endocytic hot spots, traffic within endosomes, and are targeted to the ER.
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Heusermann W
Novartis Institutes for Biomedical Research, CH-4000 Basel, Switzerland wolf.heusermann@unibas.ch nicole.meisner-kober@novartis.com.
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Hean J
Novartis Institutes for Biomedical Research, CH-4000 Basel, Switzerland Department of Physiology, Anatomy, and Genetics, University of Oxford, Oxford OX1 3QX, England, UK.
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Trojer D
Novartis Institutes for Biomedical Research, CH-4000 Basel, Switzerland.
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Steib E
Novartis Institutes for Biomedical Research, CH-4000 Basel, Switzerland.
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von Bueren S
Novartis Institutes for Biomedical Research, CH-4000 Basel, Switzerland.
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Graff-Meyer A
Friedrich-Miescher Institute for Biomedical Research, CH-4000 Basel, Switzerland.
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Genoud C
Friedrich-Miescher Institute for Biomedical Research, CH-4000 Basel, Switzerland.
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Martin K
Department of Biomedicine, University of Basel, CH-4058 Basel, Switzerland.
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Pizzato N
Novartis Institutes for Biomedical Research, CH-4000 Basel, Switzerland.
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Voshol J
Novartis Institutes for Biomedical Research, CH-4000 Basel, Switzerland.
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Morrissey DV
Novartis Institutes for Biomedical Research, Cambridge, MA 02139.
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Andaloussi SE
Department of Physiology, Anatomy, and Genetics, University of Oxford, Oxford OX1 3QX, England, UK Department of Laboratory Medicine, Karolinska Institutet, SE-141 86 Huddinge, Sweden.
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Wood MJ
Department of Physiology, Anatomy, and Genetics, University of Oxford, Oxford OX1 3QX, England, UK.
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Meisner-Kober NC
Novartis Institutes for Biomedical Research, CH-4000 Basel, Switzerland wolf.heusermann@unibas.ch nicole.meisner-kober@novartis.com.
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Published in:
- The Journal of cell biology. - 2016
English
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. After 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.
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Language
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Open access status
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bronze
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Identifiers
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Persistent URL
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https://sonar.ch/global/documents/93931
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