Linda A. Verkruyse

TL;DR: The identification, by positional candidate methods, of defects in the palmitoyl-protein thioesterase gene in all 42 Finnish INCL patients and several non-Finnish patients is reported, which results in intracellular accumulation of the polypeptide and undetectable enzyme activity in the brain of patients.

TL;DR: It is shown that COS cells take up exogenously supplied palmitoyl-protein thioesterase intracellularly and that the cellular uptake is blocked by mannose 6-phosphate, a hallmark of lysosomal enzyme trafficking.

TL;DR: While thePalmitoyl-protein thioesterase will deacylate intracellular palmitoylated proteins such as Ha-Ras and the alpha subunits of heterotrimeric G proteins, the physiologic substrates are likely to be externally oriented or secreted proteins.

TL;DR: It is demonstrated that [35S]cysteine-labeled lipid thioesters accumulate in immortalized lymphoblasts of patients with infantile neuronal ceroid lipofuscinosis, and this data support a role for palmitoyl-protein thioesterase in the lysosomal degradation of S-acylated proteins and define a major new pathway for the catabolism of acylated proteins in theLysosome.

TL;DR: A model for the formation of the storage bodies in INCL involving defective autophagocytic proteolysis is proposed and absence of PPT activity in lysosomes isolated from INCL lymphoblasts is demonstrated.