Title
Spatial regulation and the rate of signal transduction activation.
Abstract
Of the many important signaling events that take place on the surface of a mammalian cell, activation of signal transduction pathways via interactions of cell surface receptors is one of the most important. Evidence suggests that cell surface proteins are not as freely diffusible as implied by the classic fluid mosaic model and that their confinement to membrane domains is regulated. It is unknown whether these dynamic localization mechanisms function to enhance signal transduction activation rate or to minimize cross talk among pathways that share common intermediates. To determine which of these two possibilities is more likely, we derive an explicit equation for the rate at which cell surface membrane proteins interact based on a Brownian motion model in the presence of endocytosis and exocytosis. We find that in the absence of any diffusion constraints, cell surface protein interaction rate is extremely high relative to cytoplasmic protein interaction rate even in a large mammalian cell with a receptor abundance of a mere two hundred molecules. Since a larger number of downstream signaling events needs to take place, each occurring at a much slower rate than the initial activation via association of cell surface proteins, we conclude that the role of colocalization is most likely that of cross- talk reduction rather than coupling efficiency enhancement.
Year
DOI
Venue
2006
10.1371/journal.pcbi.0020044
PLOS COMPUTATIONAL BIOLOGY
Keywords
Field
DocType
signal transduction pathway,brownian motion,signal transduction,membrane protein,proteins,cytoplasm
Membrane protein,Protein–protein interaction,Exocytosis,Biology,Upstream and downstream (transduction),Cell biology,Signal transduction,Fluid mosaic model,Cell surface receptor,Endocytosis
Journal
Volume
Issue
ISSN
2
5
1553-734X
Citations 
PageRank 
References 
3
1.07
0
Authors
4
Name
Order
Citations
PageRank
Nizar N Batada1534.62
Larry A. Shepp26612.91
David O Siegmund331.07
Michael Levitt458799.00