Mutations in the CLN7 (MFSD8) gene, causes CLN7 disease, a subtype of neuronal ceroid lipofuscinosis. MFSD8 is a lysosomal transmembrane protein that transports chloride across membranes. Experimentation regarding Dictyostelium discoideum revealed that mfsd8 deficiency altered lysosomal enzyme activity. During starvation, the aggregation of mfsd8¬¬- cells was delayed, and cells formed more mounds that were smaller in size, phenotypes that were attributed to reduced cell-substrate adhesion and altered lysosomal enzymatic activities. This study examines the possible transcriptomic and secretomic basis for these phenotypes. This work generated new datasets for examining the effect of mfsd8 loss on the transcriptome and secretome. The validity of these datasets was supported by use of western blotting and RT-PCR along with a set of assays probing relevant biological processes. Together these results elucidate the biological mechanisms behind the observed phenotypes and lay the foundation for future studies to further study the cellular role of MFSD8.
Author Keywords: Battens disease, CLN7, Dictyostelium discoideum, MFSD8, Secretome, Transcriptome