Dynein Clusters into Lipid Microdomains on Phagosomes to Drive Rapid Transport toward Lysosomes.

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TitleDynein Clusters into Lipid Microdomains on Phagosomes to Drive Rapid Transport toward Lysosomes.
Publication TypeJournal Article
Year of Publication2016
AuthorsRai A, Pathak D, Thakur S, Singh S, Dubey AKumar, Mallik R
Date Published2016 Feb 11
KeywordsAnimals, Biological Transport, Cell Line, Dictyostelium, Dyneins, Glycosphingolipids, Leishmania donovani, Lysosomes, Membrane Microdomains, Mice, Phagosomes

Diverse cellular processes are driven by motor proteins that are recruited to and generate force on lipid membranes. Surprisingly little is known about how membranes control the force from motors and how this may impact specific cellular functions. Here, we show that dynein motors physically cluster into microdomains on the membrane of a phagosome as it matures inside cells. Such geometrical reorganization allows many dyneins within a cluster to generate cooperative force on a single microtubule. This results in rapid directed transport of the phagosome toward microtubule minus ends, likely promoting phagolysosome fusion and pathogen degradation. We show that lipophosphoglycan, the major molecule implicated in immune evasion of Leishmania donovani, inhibits phagosome motion by disrupting the clustering and therefore the cooperative force generation of dynein. These findings appear relevant to several pathogens that prevent phagosome-lysosome fusion by targeting lipid microdomains on phagosomes.

Alternate JournalCell
PubMed ID26853472
PubMed Central IDPMC4752818
Grant ListIA/S/11/2500255 / / Wellcome Trust / United Kingdom
WT079214MA / / Wellcome Trust / United Kingdom