Three-dimensional analysis of the 16-nm urotheilial plaque particle

The luminal surface of mouse urothelium in contact with the urine is almost entirely covered with plaques consisting of uroplakin-containing particles that form p6 hexagonal crystals with a center-to-center distance of 16 nm. A combination of quick-freeze/deep-etch images and previous negative staining data indicate that the head domain of the uroplakin particle, which is exposed without an extensive glycocalyx shield, interacts closely with the head domains of the neighbouring particles, while the membrane-embedded tail domains are farther apart, and that urothelial particles and plaques are not rigid structures as they can change their configuration in response to mechanical perturbations. Based on these data, we have constructed three-dimensional models depicting the structural organization of urothelial particles and plaques (Kachar et al., 1999). Our models suggest that the head-to-head interaction may play a key role in determining the shape and size of the urothelial plaques. These models can explain many properties of urothelial plaques including their unique shape, detergent-insolubility, and morphological changes during vesicle maturation.

Figure 1: 3-D reconstruction of a urothelial plaque. (a) (yellow) The top view of a model in which several 3D twisted-ribbon models of the head domain of the AUM particle were fit interactively in 3-D onto a two dimensional AUM stain-exclusion map which was texture mapped onto a square. (orange) The bottom view of the model showing the fitting of the models of the transmembranous (TM) portion of the AUM particle. (b) The side view of two model plaques adjoined by a hinge area illustrating that head-head interaction among neighboring AUM particles. It is hypothesize that the head-to-head interaction between neighboring AUM particles results in a bend (that is 5°out of the plane in this diagram for illustration purpose) which results in the formation of a concave plaque. While the addition of a particle to the edge of an existing plaque may be energetically favored, this is counter-balanced by local surface tension which limits the extent by which the edge of an expanding plaque can protrude from the cell surface. The balance between these two opposing forces may thus limit the maximal number of particles that can participate in forming a single plaque.

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