Mutations in the CLN7/MFSD8 gene encoding the lysosomal membrane protein
CLN7 are causative of CLN7 disease, an inherited neurodegenerative
disorder that typically affects children. To gain insight into the
pathomechanisms of CLN7 disease, we established an immortalized cell
line based on cerebellar (Cb) granule neuron precursors isolated from
Cln7-/- mice. Here, we demonstrate that Cln7-deficient
neuron-derived Cb cells display an abnormal phenotype that includes
increased size and defective outward movement of late endosomes and
lysosomes as well as impaired lysosomal exocytosis. Whereas Cln7-/-
Cb cells appeared to be autophagy-competent, loss of Cln7 resulted in
enhanced cell death under prolonged nutrient deprivation. Furthermore,
reduced cell survival of Cln7-deficient cells was accompanied by a
significantly impaired protein kinase B/Akt phosphorylation at Ser473
during long-term starvation. In summary, our data demonstrate for the
first time that the putative lysosomal transporter CLN7 is relevant for
lysosome motility and plays an important role for neuronal cell survival
under conditions of starvation.