Quality control of protein folding in extracellular space.
The pathologies of many serious human diseases are thought to develop from the effects of intra- or extracellular aggregates of non-native proteins. Inside cells, chaperone and protease systems regulate protein folding; however, little is known about any corresponding mechanisms that operate extracellularly. The identification of these mechanisms is important for the development of new disease therapies. This review briefly discusses the consequences of protein misfolding, the intracellular mechanisms that control folding and the potential corresponding extracellular control processes. Finally, a new speculative model is described, which proposes that newly discovered extracellular chaperones bind to exposed regions of hydrophobicity on non-native, extracellular proteins to target them for receptor-mediated endocytosis and intracellular, lysosomal degradation.
Yerbury
Justin J
JJ
School of Biological Sciences, University of Wollongong, Wollongong, NSW 2522, Australia. jyerbury@uow.edu.au
Stewart
Elise M
EM
Wyatt
Amy R
AR
Wilson
Mark R
MR
D000818:Animals; D005110:Extracellular Space; D006801:Humans; D008954:Models, Biological; D018832:Molecular Chaperones / Q000378:metabolism*; D017510:Protein Folding
D018832:Molecular Chaperones