CRF fellow : Gennaro Napolitano

The aim of the project “Small molecule regulators of vesicular trafficking to enhance lysosomal exocytosis in cystinosis” is to use strategies directed at upregulating the exocytic pathway in cystinotic cells, in order to improve vesicular transport, force cystine release and restore normal cell function. Our hypothesis, in fact, states that cells that have accumulated cystine share the intracellular traffic defects that characterize other lysosomal storage disorders and that correction of intracellular vesicular trafficking would lead to improvement of the pathological conditions. In my previous fellowship report I showed that CTNS-deficient cells have enlarged and increased number of lysosomes, which correlated with impaired lysosomal trafficking in these cells. Importantly, overexpression of the constitutively active form of the small GTPase Rab27a (Rab27aQ78L) was able to rescue proper lysosomal trafficking in CTNS-deficient cells.