| Autor: |
Lai, F.P.L., Mody, S.M., Yung, L.Y., Kam, J.Y.M., Pang, C.S., Pang, S.F., Wong, Y.H. |
| Předmět: |
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| Zdroj: |
Journal of Neurochemistry; 3/1/2002, Vol. 80 Issue 5, p736-745, 10p |
| Abstrakt: |
The pineal neurohormone melatonin modulates a variety of physiological processes through different receptors. It has recently been reported that the cloned melatonin receptors (MT1, MT2 and Mel1c) exhibit differential abilities to stimulate phospholipase C (PLC) via G[sub 16]. Here we examined the molecular basis of such differences in melatonin receptor signaling. Coexpression of MT1 or MT2 with the α subunit of G[sub 16] (Gα[sub 16]) allowed COS-7 cells to accumulate inositol phosphates in response to 2-iodomelatonin. In contrast, Mel1c did not activate Gα[sub 16] even though its expression was demonstrated by radioligand binding and agonist-induced inhibition of adenylyl cyclase. As Mel1c possesses an exceptionally large C-terminal tail, we further asked if this structural feature prevented productive coupling to Gα[sub 16]. Eleven chimeric melatonin or mutant receptors were constructed by swapping all or part of the C-terminal tail between MT1, MT2 and Mel1c. All chimeras were fully capable of binding 2-[[sup 125]I]iodomelatonin and inhibiting adenylyl cyclase. Chimeras containing the full-length Mel1c tail were incapable of activating Gα[sub 16], while those that contained the complete C-terminal region of either MT1 or MT2 stimulated PLC. Incorporation of the extra portion of the C-terminal tail of Mel1c to either MT1 or MT2 completely abolished the chimeras' ability to stimulate PLC via Gα[sub 16]. In contrast, trunc- ation of the C-terminal tail of Mel1c allowed interaction with Gα[sub 16]. Our results suggest that Gα[sub 16] can discern structural differences amid the three melatonin receptors and provide evidence for functional distinction of Mel1c from MT1 and MT2 receptors. [ABSTRACT FROM AUTHOR] |
| Databáze: |
Complementary Index |
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