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Citation
Venkatachalam, K., Long, A.A., 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(5): 838--851.
FlyBase ID
FBrf0206372
Publication Type
Research paper
Abstract

Disruption of the Transient Receptor Potential (TRP) mucolipin 1 (TRPML1) channel results in the neurodegenerative disorder mucolipidosis type IV (MLIV), a lysosomal storage disease with severe motor impairments. The mechanisms underlying MLIV are poorly understood and there is no treatment. Here, we report a Drosophila MLIV model, which recapitulates the key disease features, including abnormal intracellular accumulation of macromolecules, motor defects, and neurodegeneration. The basis for the buildup of macromolecules was defective autophagy, which resulted in oxidative stress and impaired synaptic transmission. Late-apoptotic cells accumulated in trpml mutant brains, suggesting diminished cell clearance. The accumulation of late-apoptotic cells and motor deficits were suppressed by expression of trpml(+) in neurons, glia, or hematopoietic cells. We conclude that the neurodegeneration and motor defects result primarily from decreased clearance of apoptotic cells. Since hematopoietic cells in humans are involved in clearance of apoptotic cells, our results raise the possibility that bone marrow transplantation may limit the progression of MLIV.

PubMed ID
PubMed Central ID
PMC2649760 (PMC) (EuropePMC)
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    Language of Publication
    English
    Additional Languages of Abstract
    Parent Publication
    Publication Type
    Journal
    Abbreviation
    Cell
    Title
    Cell
    Publication Year
    1974-
    ISBN/ISSN
    0092-8674
    Data From Reference
    Aberrations (2)
    Alleles (17)
    Genes (12)
    Human Disease Models (2)
    Natural transposons (1)
    Insertions (5)
    Experimental Tools (1)
    Transgenic Constructs (10)