Department of Cell Biology
Harvard Medical School
(Asbstract of JCB paper, in press) How can organelles communicate by bidirectional vesicle transport and yet maintain different protein compositions? We show by mathematical modeling that a minimal system, in which the basic variables are cytosolic coats for vesicle budding and membrane-bound SNAREs (soluble N-ethylmaleimide-sensitive factor attachment protein receptors) for vesicle fusion, is sufficient to generate stable, non-identical compartments. A requirement for establishing and maintaining distinct compartments is that each coat preferentially packages certain SNAREs during vesicle budding. Vesicles fuse preferentially with the compartment that contains the highest concentration of cognate SNAREs, thus further increasing these SNAREs. The stable steady state is the result of a balance between this autocatalytic SNARE accumulation in a compartment and the distribution of SNAREs between compartments by vesicle budding. The resulting non-homogeneous SNARE distribution generates coat-specific vesicle fluxes that determine the size of compartments. With non-identical compartments established in this way, the localization and cellular transport of cargo proteins can be explained simply by their affinity for coats.