Association of sequestered beta-adrenergic receptors with the plasma membrane: a novel mechanism for receptor down regulation.
Association of sequestered beta-adrenergic receptors with the plasma membrane: a novel mechanism for receptor down regulation.
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隔离的β-肾上腺素受体与质膜的关联：受体下调的新机制。
DOI：
10.1016/0024-3205(84)90359-x
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发表时间：
1984
期刊：
影响因子：
6.1
通讯作者：
Lefkowitz,RJ
中科院分区：
文献类型：
--
作者：
Strader,CD;Sibley,DR;Lefkowitz,RJ
青蛙红细胞长期暴露于β-肾上腺素能激动剂导致腺苷酸环化酶对异丙肾上腺素的反应性脱敏，并伴有“下调”，即细胞表面β-肾上腺素能受体数量减少。当通过细胞的渗透裂解制备蛙红细胞质膜时，在脱敏过程中从细胞表面丢失的受体可以在“轻膜部分”中恢复，所述“轻膜部分”通过将细胞胞质溶胶在158，000 × g下浸泡1小时获得。这些受体与含有腺苷酸环化酶和鸟嘌呤核苷酸调节蛋白的质膜部分隔离开。然而，如果通过温和的冻融程序破坏脱敏的青蛙红细胞，则可以证明隔离的β-肾上腺素能受体与质膜物理相关。通常，以这种方式制备的质膜不表现出显着的下调，尽管异丙肾上腺素刺激的腺苷酸环化酶活性的衰减。在这些条件下，来自对照和脱敏制剂的β-肾上腺素能受体在蔗糖密度梯度上共迁移到与质膜标记物腺苷酸环化酶完全相同的位置。相反，当将来自经免疫裂解的脱敏细胞的膜在蔗糖梯度上分级分离时，下调的受体被隔离在几乎不进入梯度并且与腺苷酸环化酶活性物理分离的轻膜级分中。这些数据与受体下调的新机制一致，该机制似乎涉及将β-肾上腺素能受体从细胞表面隔离到与质膜保持物理关联的膜隔室中。
Chronic exposure of frog erythrocytes to β-adrenergic agonists leads to desensitization of the responsiveness of adenylate cyclase to isoproterenol and is accompanied by “down-regulation”, a decrease in the number of β-adrenergic receptors on the cell surface. When frog erythrocyte plasma membranes are prepared by osmotic lysis of cells, the receptors lost from the cell surface during desensitization can be recovered in a “light membrane fraction”, obtained by centrifuging the cell cytosol at 158,000 × g for 1 hr. These receptors are sequestered away from the plasma membrane fraction which contains the adenylate cyclase and the guanine nucleotide regulatory protein. If desensitized frog erythrocytes are disrupted by gentler freeze/-thaw procedures, however, the sequestered β-adrenergic receptors can be demonstrated to be physically associated with the plasma membrane. Typically, plasma membranes prepared in this fashion do not demonstrate a significant down regulation despite attenuation of isoproterenol-stimulated adenylate cyclase activity. Under these conditions, β-adrenergic receptors from control and desensitized preparations co-migrate on sucrose density gradients in exactly the same place as the plasma membrane marker, adenylate cyclase. In contrast, when membranes from osmotically lysed desensitized cells are fractionated on sucrose gradients the down regulated receptors are sequestered in a light membrane fraction which barely enters the gradient and which is physically separated from adenylate cyclase activity. The data are consistent with a novel mechanism of receptor down-regulation which appears to involve the sequestration of the β-adrenergic receptors away from the cell surface into a membrane compartment which remains physically associated with the plasma membrane.
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儿茶酚胺诱导膜结合β-肾上腺素能受体沉降行为的改变。
DOI：
10.1126/science.6254143
发表时间：
1980
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Harden,TK;Cotton,CU;Waldo,GL;Lutton,JK;Perkins,JP
通讯作者：
Perkins,JP
儿茶酚胺特异性腺苷酸环化酶脱敏。
影响因子：
4.8
作者：
Y. F. Su;T. Harden;J. Perkins
通讯作者：
J. Perkins
进一步的证据表明，β-肾上腺素能敏感的腺苷酸环化酶的脱敏分两个步骤进行。
影响因子：
4.8
作者：
V. Homburger;M. Lucas;B. Cantau;J. Barabé;J. Pénit;J. Bockaert
通讯作者：
J. Bockaert
DOI：
10.1083/jcb.75.2.528
发表时间：
1977-11
期刊：
The Journal of cell biology
影响因子：
--
作者：
Hopkins CR;Gregory H
通讯作者：
Gregory H
用（负）-[3-H]阿普洛尔鉴定青蛙红细胞中腺苷酸环化酶偶联的 β-肾上腺素能受体。
影响因子：
4.8
作者：
C. Mukherjee;M. Caron;M. Coverstone;R. Lefkowitz
通讯作者：
R. Lefkowitz