The neurodegenerative disorder mucolipidosis type IV (MLIV) is an early childhood lysosomal storage disease linked to disruption of the transient receptor potential mucolipin 1 (TRPML1) channel. Affected patients experience severe motor deficits and mental retardation, as well as retinal degeneration. In this paper, Venkatachalam et al. present a Drosophila model of MLIV in which mutation of TRPML1 causes locomotor deficits, progressive neurodegeneration and aberrant lysosomal storage. Additional analysis of the flies revealed that decreased apoptotic cell clearance results in oxidative stress and impairment of neuronal signaling. The study provides a new understanding of the mechanism underlying MLIV, as well as leads for potential therapies.
Venkatachalam K, Long AA, Elsaesser R, Nikolaeva D, Broadie K, Montell C. (2008). Motor deficit in a drosophila model of mucolipidosis type IV due to defective clearance of apoptotic cells. Cell 135, 838– 851.
