Quantitative properties and receptor reserve of the IP(3) and calcium branch of G(q)-coupled receptor signaling.
Quantitative properties and receptor reserve of the IP(3) and calcium branch of G(q)-coupled receptor signaling.
复制标题
DOI：
10.1085/jgp.201210886
复制
发表时间：
2013-05
期刊：
影响因子：
--
通讯作者：
Hille B
中科院分区：
文献类型：
--
作者：
Dickson EJ;Falkenburger BH;Hille B
Gq偶联质膜受体激活磷脂酶C（PLC），其将膜磷脂酰肌醇4，5-二磷酸（PIP 2）水解成第二信使肌醇1，4，5-三磷酸（IP 3）和二酰基甘油（DAG）。这导致钙释放，蛋白激酶C（PKC）激活，有时PIP 2耗尽。为了了解这些分歧信号的机制，并确定这些信号中的哪一个负责抑制KCNQ 2/3（KV7.2/7.3）钾通道，我们监测了单个活细胞中PIP 2，IP 3和钙的水平。在我们的配套论文中监测了DAG和PKC（Falkenburger et al. 2013. http：//dx.doi.org/10.1085/jgp.201210887）。结果扩展了我们以前的动力学模型的Gq偶联受体信号IP 3和钙。我们发现，饱和浓度的尿苷5′-三磷酸（UTP; 100 µM）激活低丰度内源性P2 Y2受体可导致钙释放，但不会导致PIP 2耗竭。通过10 µM Oxo-M激活过表达的M1毒蕈碱受体导致类似的钙释放，但也消耗PIP 2。KCNQ 2/3通道被Oxo-M抑制（85%），但不被UTP抑制（<1%）。这些差异可以完全归因于受体丰度的差异。即使在PIP 2被过表达的诱导型磷脂酰肌醇5-磷酸酶部分耗尽后，也可以引起全振幅钙反应，这表明非常少量的IP 3足以引起全钙释放。因此，弱PLC激活可以引起强钙信号，而没有净PIP 2消耗或KCNQ 2/3通道抑制。
Gq-coupled plasma membrane receptors activate phospholipase C (PLC), which hydrolyzes membrane phosphatidylinositol 4,5-bisphosphate (PIP2) into the second messengers inositol 1,4,5-trisphosphate (IP3) and diacylglycerol (DAG). This leads to calcium release, protein kinase C (PKC) activation, and sometimes PIP2 depletion. To understand mechanisms governing these diverging signals and to determine which of these signals is responsible for the inhibition of KCNQ2/3 (KV7.2/7.3) potassium channels, we monitored levels of PIP2, IP3, and calcium in single living cells. DAG and PKC are monitored in our companion paper (Falkenburger et al. 2013. J. Gen. Physiol. http://dx.doi.org/10.1085/jgp.201210887). The results extend our previous kinetic model of Gq-coupled receptor signaling to IP3 and calcium. We find that activation of low-abundance endogenous P2Y2 receptors by a saturating concentration of uridine 5′-triphosphate (UTP; 100 µM) leads to calcium release but not to PIP2 depletion. Activation of overexpressed M1 muscarinic receptors by 10 µM Oxo-M leads to a similar calcium release but also depletes PIP2. KCNQ2/3 channels are inhibited by Oxo-M (by 85%), but not by UTP (<1%). These differences can be attributed purely to differences in receptor abundance. Full amplitude calcium responses can be elicited even after PIP2 was partially depleted by overexpressed inducible phosphatidylinositol 5-phosphatases, suggesting that very low amounts of IP3 suffice to elicit a full calcium release. Hence, weak PLC activation can elicit robust calcium signals without net PIP2 depletion or KCNQ2/3 channel inhibition.
登录
查看更多内容
影响因子：
5.5
作者：
Murata, Yoshimichi;Okamura, Yasushi
通讯作者：
Okamura, Yasushi
影响因子：
5.5
作者：
Balla, Tamas
通讯作者：
Balla, Tamas
影响因子：
5.3
作者：
Gamper, N;Reznikov, V;Shapiro, MS
通讯作者：
Shapiro, MS
DOI：
10.1073/pnas.92.12.5317
发表时间：
1995-06-06
影响因子：
11.1
作者：
NAKANISHI, S;CATT, KJ;BALLA, T
通讯作者：
BALLA, T
影响因子：
7.8
作者：
Matsu-ura, Toru;Michikawa, Takayuki;Inoue, Takafumi;Miyawaki, Atsushi;Yoshida, Manabu;Mikoshiba, Katsuhiko
通讯作者：
Mikoshiba, Katsuhiko