[Adult GM1 gangliosidosis--biochemical studies--1]

To address the pathogenesis of GM1 gangliosidosis, especially adult form, intracellular signal transduction pathway of EGF in skin fibroblasts from patients with this disorder was examined. For this purpose, skin fibroblasts from 2 different patients with adult form of the disorder and from 4 different normal controls were used. The results showed that 1) EGF-receptor autophosphorylation was diminished in skin fibroblasts from patients with altered time course of phosphorylation-dephosphorylation reaction. 2) The amount of EGF-receptor protein was decreased in cells from patients compared with that of controls. 3) 125I-EGF binding + internalization studies revealed decreased rate of EGF binding and internalization in patient cells. 4) Ribosomal S6 protein phosphorylation was strongly enhanced in naive cells from patients, but the reactivity to EGF was diminished compared with control cells. These data strongly suggest that patient fibroblasts have abnormalities in the intracellular signal transduction pathway of EGF. This paper is considered to be the first report demonstrating abnormalities in EGF-signal transducing system in human disorders.