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Logo of jbcThe Journal of Biological Chemistry
 
J Biol Chem. 2012 September 21; 287(39): 32874.
PMCID: PMC3463361

Neurodegeneration and Neuronal Migration Defect Caused by Disruption in Vesicle Transport♦

Ablation of Vacuole Protein Sorting 18 (Vps18) Gene Leads to Neurodegeneration and Impaired Neuronal Migration by Disrupting Multiple Vesicle Transport Pathways to Lysosomes

♦ See referenced article, J. Biol. Chem. 2012, 287, 32861–32873

Neurons are dependent on intracellular vesicle transport pathways for their development and survival. In lower organisms like Drosophila, the Vps-C complex regulates many vesicle transport pathways to the lysosome, but the complex's function in mammals is unclear. In this Paper of the Week, a team led by Wufan Tao at Fudan University in China and Tian Xu at the Howard Hughes Medical Institute and Yale University School of Medicine investigated the function of Vps18, the main member of the Vps-C complex, in mice. Animals missing the Vps18 gene suffered severe neurodegeneration and defects in neural migration. The investigators showed that the neurodegeneration was caused by the disruption of multiple vesicle transport pathways; the migration defect resulted from the accumulation of β1 integrin on cell surfaces in Vps18-deficient brains. The authors concluded, “Our results demonstrate important roles of Vps18 in neuron survival and migration, which are disrupted in multiple neural disorders.”

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Histological analysis of the Vps18 CKO hippocampus in this study indicated neuronal migration defect (split CA3 region) at P1 and complete disruption of the morphological structures at P10.


Articles from The Journal of Biological Chemistry are provided here courtesy of American Society for Biochemistry and Molecular Biology