AJP - Regulatory, Integrative and Comparative Physiology, Vol 247, Issue 5 768-R779, Copyright © 1984 by American Physiological Society
Receptor-mediated endocytosis: a model and its implications for experimental analysis
M. Gex-Fabry and C. DeLisi
We present a mathematical model for analyzing, simulating, and quantitating
the dynamic and steady-state characteristics of receptor-mediated
endocytosis. The basic processes considered by the model are
ligand-receptor binding, diffusion of receptors and ligand-receptor
complexes in the plane of the membrane toward and away from coated pits,
binding of ligand-receptor complexes to coated pit proteins, endocytosis of
coated pit contents, degradation of ligand, and recycling of undegraded
receptors. The model accounts quantitatively for a wide variety of kinetic
data and makes new predictions about steady-state characteristics. We show
that for homogeneous receptors the slope of the Scatchard plot is not
necessarily constant but can have a positive or negative derivative,
depending on the concentration of coated pit proteins and their reactivity.
This finding suggests that binding data, which show linear and concave
curves, might be explainable be a simple coated pit-related mechanism.
Similarly the relationship between the x-intercept and the number of
receptors is also affected by kinetic parameters controlling endocytosis.
We briefly discuss these results in terms of possible mechanisms for the
action of tumor promoters, the large variations in receptor number and
affinity in the literature, and methods for quantitative characterization
of parameters.
