Figure 6.

Model for the Bidirectional to Retrograde Switch in Phagosome Transport

An early phagosome with dynein and kinesin motors is shown. Motors are randomly distributed on the surface. Some dyneins are shown engaged to a MT at the bottom through Rab5. A kinesin is also engaged to the MT. This situation results in force balanced bidirectional motion interspersed by a tug of war between kinesin and dynein (opposing red and green arrows of equal size). Phagosomes acquire membrane cholesterol as they mature because of physical interactions with cholesterol-rich late endosomes (red spheres). Late phagosomes now develop stable cholesterol-rich microdomains (three microdomains are shown). Microdomain formation is likely facilitated by Rab7-GTP. Dynein, along with Rab7, clusters into microdomains to form “force-generating platforms” where multiple dyneins are in close proximity and ordered orientation. This generates large persistent force to drive minus-end-directed transport of the phagosome (large green arrow). Kinesin may possibly be excluded from such microdomains (remains to be investigated). Note that the total number of motors (dynein or kinesin) remains almost unchanged between EPs and LPs.