Is an ability of SNX-BAR proteins to associate with molecular motors important in longitudinal force generation during membrane fission, and long-range carrier transport between donor and recipient membranes?
A central feature of any membrane trafficking pathway is the need to couple the cargo-enriched sub-domain of the donor compartment to molecular motors and other forms of force generation in order to assist the fission and subsequent transport of the cargo ladened carrier to the recipient membrane. Evidence linking SNX-BARs with molecular motors has emerged from the demonstration that SNX4 forms a complex with the minus-end directed microtubule motor dynein. This interaction is important for the long-range transport of transferrin receptor-enriched carriers from the peripheral early endosome to the juxtanuclear ERC - effectively co-ordinating transferrin receptor sorting with the long range transport of receptor enriched carriers. Whether other SNX-BARs couple to molecular motors, and thereby co-ordinate tubular-based endosomal sorting with carrier formation and transport is an intriguing issue.
We are:
- screening other SNX-BARs for direct or indirect association with molecular motors.
- examining if the association with motors is required to assist membrane tubulation, and the generation of longitudinal force required for membrane fission.
- establishing how the formation of membrane tubules, scaffolding of sorting complexes, and coupling to force generation are temporally co-ordinated and regulated in response to cellular requirements.