Internalization and down-regulation of muscarinic acetylcholine receptors in cerebellar granule cells of tenascin-gene deficient mice.
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 microM) 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.
Fukamauchi
F
F
Department of Molecular Medical Science, Medical Research Institute, Tokyo Medical and Dental University, Japan. ff.epi@mri.tmd.ac.jp
Aihara
O
O
Kusakabe
M
M
D000818:Animals; D002217:Carbachol / Q000494:pharmacology; D002462:Cell Membrane / Q000378:metabolism; D002531:Cerebellum / Q000378:metabolism*; D018679:Cholinergic Agonists / Q000494:pharmacology; D015536:Down-Regulation; D051379:Mice; D018345:Mice, Knockout; D019832:N-Methylscopolamine / Q000378:metabolism; D017239:Paclitaxel / Q000494:pharmacology; D011813:Quinuclidinyl Benzilate / Q000378:metabolism; D011976:Receptors, Muscarinic / Q000378:metabolism*; D019063:Tenascin / Q000172:deficiency* / Q000235:genetics / Q000502:physiology; D014316:Tritium
D018679:Cholinergic Agonists; D011976:Receptors, Muscarinic; D019063:Tenascin; D014316:Tritium; D011813:Quinuclidinyl Benzilate; D002217:Carbachol; D017239:Paclitaxel; D019832:N-Methylscopolamine