Internalization and down-regulation of muscarinic acetylcholine receptors in cerebellar granule cells of tenascin-gene deficient mice

• Published in: Neurochemistry international 2000-02, Vol.36 (2), p.153-158
• Main Authors: Fukamauchi, Fumihiko, Aihara, Okihiko, Kusakabe, Moriaki
• Format: Article
• Language: English
• Subjects: Animals; Biological and medical sciences; Carbachol - pharmacology; Cell Membrane - metabolism; Central nervous system; Central neurotransmission. Neuromudulation. Pathways and receptors; Cerebellum - metabolism; Cholinergic Agonists - pharmacology; Down-Regulation; Fundamental and applied biological sciences. Psychology; Mice; Mice, Knockout; N-Methylscopolamine - metabolism; Paclitaxel - pharmacology; Quinuclidinyl Benzilate - metabolism; Receptors, Muscarinic - metabolism; Tenascin - deficiency; Tenascin - genetics; Tenascin - physiology; Tritium; Vertebrates: nervous system and sense organs
• ISSN: 0197-0186; 1872-9754
• DOI: 10.1016/S0197-0186(99)00106-0

The expression of tenascin-C on oligodendrocytes parallels the migration of granule cells in the developing cerebellum, indicating a role for tenascin-C as a guide for granule neurons to find their proper locations. In this study, cultured cerebellar granule neurons from tenascin-C-knockout mice were used to examine the role of tenascin-C in agonist-induced muscarinic acetylcholine receptor down-regulation. Exposure of granule cells from wild-type or tenascin-C-negative mice to the muscarinic acetylcholine receptor agonist carbachol (1 mM) resulted in normal sequestration of cell-surface muscarinic acetylcholine receptors as assessed by [ 3H] N-methylscopolamine binding; however, down-regulation of total muscarinic acetylcholine receptors, measured with [ 3H]quinuclidinyl benzilate, was inhibited in granule cells from tenascin-C-negative mice. Remarkably, incubation of the tenascin-C-negative cells with the microtubule stabilizer taxol (10 μM) restored down-regulation of total muscarinic acetylcholine receptors to normal levels. We speculate that agonist-induced down-regulation of muscarinic acetylcholine receptors is functionally associated with tenascin-C-regulated microtubule structures in the developing cerebellum.