title: Dynein Clusters into Lipid Microdomains on Phagosomes to Drive Rapid Transport toward Lysosomes.
abstract: 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.
authors: Department of Biological Sciences, Tata Institute of Fundamental Research, Homi Bhabha Road, Mumbai 400005, India.
authors: Ashim
authors: A
authors: Rai
authors: Department of Biological Sciences, Tata Institute of Fundamental Research, Homi Bhabha Road, Mumbai 400005, India.
authors: Divya
authors: D
authors: Pathak
authors: Department of Biological Sciences, Tata Institute of Fundamental Research, Homi Bhabha Road, Mumbai 400005, India.
authors: Shreyasi
authors: S
authors: Thakur
authors: Department of Biological Sciences, Tata Institute of Fundamental Research, Homi Bhabha Road, Mumbai 400005, India.
authors: Shampa
authors: S
authors: Singh
authors: Department of Biological Sciences, Tata Institute of Fundamental Research, Homi Bhabha Road, Mumbai 400005, India.
authors: Alok Kumar
authors: AK
authors: Dubey
authors: Department of Biological Sciences, Tata Institute of Fundamental Research, Homi Bhabha Road, Mumbai 400005, India. Electronic address: roop@tifr.res.in.
authors: Roop
authors: R
authors: Mallik
mesh_terms: D000818:Animals; D001692:Biological Transport; D002460:Cell Line; D004023:Dictyostelium / Q000166:cytology; D004398:Dyneins / Q000378:metabolism; D006028:Glycosphingolipids / Q000378:metabolism; D007893:Leishmania donovani / Q000166:cytology* / Q000378:metabolism*; D008247:Lysosomes / Q000378:metabolism*; D021962:Membrane Microdomains / Q000378:metabolism; D051379:Mice; D010588:Phagosomes / Q000378:metabolism*
chemical_list: D006028:Glycosphingolipids; C008290:lipophosphonoglycan; D004398:Dyneins