An adaptable standard for protein export from the endoplasmic reticulum.
To provide an integrated view of endoplasmic reticulum (ER) function in protein export, we have described the interdependence of protein folding energetics and the adaptable biology of cellular protein folding and transport through the exocytic pathway. A simplified treatment of the protein homeostasis network and a formalism for how this network of competing pathways interprets protein folding kinetics and thermodynamics provides a framework for understanding cellular protein trafficking. We illustrate how folding and misfolding energetics, in concert with the adjustable biological capacities of the folding, degradation, and export pathways, collectively dictate an adaptable standard for protein export from the ER. A model of folding for export (FoldEx) establishes that no single feature dictates folding and transport efficiency. Instead, a network view provides insight into the basis for cellular diversity, disease origins, and protein homeostasis, and predicts strategies for restoring protein homeostasis in protein-misfolding diseases.
Wiseman
R Luke
RL
Department of Chemistry, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA.
Powers
Evan T
ET
Buxbaum
Joel N
JN
Kelly
Jeffery W
JW
Balch
William E
WE
D004721:Endoplasmic Reticulum / Q000378:metabolism*; D005089:Exocytosis / Q000502:physiology; D006706:Homeostasis; D008962:Models, Theoretical; D018832:Molecular Chaperones / Q000378:metabolism; D017510:Protein Folding; D021381:Protein Transport / Q000502:physiology*; D011506:Proteins / Q000737:chemistry / Q000378:metabolism; D013816:Thermodynamics
D018832:Molecular Chaperones; D011506:Proteins