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Restoration of proper trafficking to the cell surface for membrane proteins harboring cysteine mutations.

ABSTRACT: A common phenotype for many genetic diseases is that the cell is unable to deliver full-length membrane proteins to the cell surface. For some forms of autism, hereditary spherocytosis and color blindness, the culprits are single point mutations to cysteine. We have studied two inheritable cysteine mutants of cyclic nucleotide-gated channels that produce achromatopsia, a common form of severe color blindness. By taking advantage of the reactivity of cysteine's sulfhydryl group, we modified these mutants with chemical reagents that attach moieties with similar chemistries to the wild-type amino acids' side chains. We show that these modifications restored proper delivery to the cell membrane. Once there, the channels exhibited normal functional properties. This strategy might provide a unique opportunity to assess the chemical nature of membrane protein traffic problems.

SUBMITTER: Lopez-Rodriguez A

PROVIDER: S-EPMC3474720 | biostudies-literature | 2012

REPOSITORIES: biostudies-literature

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Restoration of proper trafficking to the cell surface for membrane proteins harboring cysteine mutations.

Lopez-Rodriguez Angelica A Holmgren Miguel M

PloS one 20121017 10

A common phenotype for many genetic diseases is that the cell is unable to deliver full-length membrane proteins to the cell surface. For some forms of autism, hereditary spherocytosis and color blindness, the culprits are single point mutations to cysteine. We have studied two inheritable cysteine mutants of cyclic nucleotide-gated channels that produce achromatopsia, a common form of severe color blindness. By taking advantage of the reactivity of cysteine's sulfhydryl group, we modified these ...[more]

PMID: 23082193

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