Model for transformations of the clathrin lattice in the coated vesicle pathway.
Transport of receptors by the coated vesicle pathway entails assembly of clathrin triskelions into a lattice in conjunction with receptors in a membrane. The processes by which the receptors are concentrated, the lattice is assembled, transformed into a cage during vesiculation, and subsequently removed from pinched off vesicles are not understood in regard to mechanism, energetics or control. Tubulin and actin assembly are looked to for analogies applicable to clathrin. The present model supposes that clathrin assembly is energy linked and can be described by kinetic equations of the same general form as those for treadmilling in linear polymers. The coat lattice assembles in a steady state involving the degradation of a high energy form of the clathrin triskelions. Diffuse endocytosis receptors are assumed to be associated with individual triskelions and to be able to trigger clustering and coated pit formation by influencing the assembly kinetics of the bound triskelions. A generalization of the treadmilling scheme is proposed by which the kinetic parameters associated with clathrin polymerization can shift simultaneously for an entire lattice to favor alternatively net assembly or disassembly. This shift is effected by a coordinated conversion of the lattice bound receptors. The conversion of the receptors in turn depends on some global property of the membrane compartments (arguably pH, calcium concentration or transmembrane voltage) which is likely to change as a consequence of vesiculation. Thereby, lattice disassembly can be coordinated with the topological conversion from coated pit to coated vesicle.
D000244:Adenosine Diphosphate / Q000378:metabolism; D000255:Adenosine Triphosphate / Q000378:metabolism; D002966:Clathrin / Q000378:metabolism*; D003034:Coated Pits, Cell-Membrane / Q000378:metabolism*; D004705:Endocytosis; D011992:Endosomes / Q000378:metabolism*; D007700:Kinetics; D008954:Models, Biological; D013816:Thermodynamics
D002966:Clathrin; D000244:Adenosine Diphosphate; D000255:Adenosine Triphosphate