Loss-of-function mutations in REP-1 affect intracellular vesicle transport in fibroblasts and monocytes of CHM patients

Choroideremia (CHM) is a progressive X-linked retinopathy caused by mutations in the CHM gene, which encodes Rab escort protein-1 (REP-1), an escort protein involved in the prenylation of Rabs. Under-prenylation of certain Rabs, as a result of loss of function mutations in REP-1, could affect vesicular trafficking, exocytosis and secretion. To evaluate this hypothesis, intracellular vesicle transport, lysosomal acidification and rates of proteolytic degradation were studied in monocytes (CD14+ fraction) and primary skin fibroblasts from the nine age-matched controls and thirteen CHM patients carrying 10 different loss-of-function mutations.

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Strunnikova NV, Barb J, Sergeev YV, Thiagarajasubramanian A, Silvin C, Munson PJ, Macdonald IM