A Bystander Mechanism Explains the Specific Phenotype of a Broadly Expressed Misfolded Protein.

ABSTRACT: Misfolded proteins in transgenic models of conformational diseases interfere with proteostasis machinery and compromise the function of many structurally and functionally unrelated metastable proteins. This collateral damage to cellular proteins has been termed 'bystander' mechanism. How a single misfolded protein overwhelms the proteostasis, and how broadly-expressed mutant proteins cause cell type-selective phenotypes in disease are open questions. We tested the gain-of-function mechanism of a R37C folding mutation in an endogenous IGF-like C.elegans protein DAF-28. DAF-28(R37C) is broadly expressed, but only causes dysfunction in one specific neuron, ASI, leading to a distinct developmental phenotype. We find that this phenotype is caused by selective disruption of normal biogenesis of

SUBMITTER: Klabonski L 

PROVIDER: S-EPMC5142776 | biostudies-literature | 2016 Dec

REPOSITORIES: biostudies-literature