First published online October 24, 2007
Journal of Cell Science 120, 2102e (2007)
© The Company of Biologists Limited
Lysosomal hideaway for ATP receptors
Extracellular ATP regulates biological processes throughout the nervous, immune and circulatory systems. Its effects are mediated by P2 purinergic receptors in the plasma membrane, including the P2X4 receptor, a ligand-gated ion channel. On p. 3838, Ruth Murrell-Lagnado and colleagues report that lysosomal sequestration and exocytosis regulate this receptor. They show that endogenous P2X4 receptors in rat microglia, endothelial cells and macrophages localize mainly to lysosomes. A dileucine motif and a tyrosine-based endocytic motif control lysosomal targeting, the authors report, and N-linked glycans protect the receptors from degradation once they arrive in lysosomes. The authors also show that, during phagocytosis, P2X4 receptors accumulate in the phagosome membrane, which suggests a function for them in intracellular membranes. By contrast, after stimulation of lysosomal exocytosis, the receptors (and the lysosomal marker LAMP-1) return to the cell surface and stimulate P2X4-mediated currents across the plasma membrane. Thus, the authors conclude, lysosome-resident P2X4 receptors provide a pool of functional receptors that can be mobilized to upregulate cellular responsiveness to extracellular ATP.
Related articles in JCS:
- Regulation of P2X4 receptors by lysosomal targeting, glycan protection and exocytosis
- Omar S. Qureshi, Anbalakan Paramasivam, Jowie C. H. Yu, and Ruth D. Murrell-Lagnado
JCS 2007 120: 3838-3849.
[Abstract]
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