Palmitoyl protein thioesterase (PPT) localizes into synaptosomes and synaptic vesicles in neurons: implications for infantile neuronal ceroid lipofuscinosis (INCL)

A deficiency of palmitoyl protein thioesterase (PPT) leads to the neurodege nerative disease infantile neuronal ceroid lipofuscinosis (INCL), which is characterized by an almost complete loss of cortical neurons. PPT expressed in COS-1 cells is recognized by the mannose-6-phosphate receptor (M6PR) an d is routed to lysosome, but a substantial fraction of PPT is secreted. We have here determined the neuronal localization of PPT by confocal microscop y, cryoimmunoelectron microscopy and cell fractionation. In mouse primary n eurons and brain tissue, PPT is localized in synaptosomes and synaptic vesi cles but not in lysosomes, Furthermore, in polarized epithelial Caco-2 cell s, PPT is localized exclusively to the basolateral site, in contrast to the classical lysosomal enzyme, aspartylglucosaminidase (AGA), which is locali zed in the apical site. The current data imply that PPT has a role outside the lysosomes in the brain and may be associated with synaptic functioning. This finding operas a new route to study the neuropathological events asso ciated with INCL.