A model for the self-organization of exit sites in the endoplasmic reticulum.
Exit sites (ES) are specialized domains of the endoplasmic reticulum (ER) at which cargo proteins of the secretory pathway are packaged into COPII-coated vesicles. Although the essential COPII proteins (Sar1p, Sec23p-Sec24p, Sec13p-Sec31p) have been characterized in detail and their sequential binding kinetics at ER membranes have been quantified, the basic processes that govern the self-assembly and spatial organization of ERES have remained elusive. Here, we have formulated a generic computational model that describes the process of formation of ERES on a mesoscopic scale. The model predicts that ERES are arranged in a quasi-crystalline pattern, while their size strongly depends on the cargo-modulated kinetics of COPII turnover - that is, a lack of cargo leads to smaller and more mobile ERES. These predictions are in favorable agreement with experimental data obtained by fluorescence microscopy. The model further suggests that cooperative binding of COPII components, for example mediated by regulatory proteins, is a key factor for the experimentally observed organism-specific ERES pattern. Moreover, the anterograde secretory flux is predicted to grow when the average size of ERES is increased, whereas an increase in the number of (small) ERES only slightly alters the flux.
Heinzer
Stephan
S
Cellular Biophysics Group (BIOMS), German Cancer Research Center, Bioquant Center, Im Neuenheimer Feld 267, D-69120 Heidelberg, Germany.
Wörz
Stefan
S
Kalla
Claudia
C
Rohr
Karl
K
Weiss
Matthias
M
D000818:Animals; D016466:CHO Cells; D022181:COP-Coated Vesicles / Q000378:metabolism; D003198:Computer Simulation; D006224:Cricetinae; D003412:Cricetulus; D004058:Diffusion; D004721:Endoplasmic Reticulum / Q000502:physiology*; D005069:Evaluation Studies as Topic; D049452:Green Fluorescent Proteins; D007091:Image Processing, Computer-Assisted; D007700:Kinetics; D008856:Microscopy, Fluorescence; D008954:Models, Biological; D010316:Particle Size; D011237:Predictive Value of Tests; D022142:Secretory Vesicles / Q000502:physiology
D049452:Green Fluorescent Proteins