β-Arrestin1 and 2 differentially regulate PACAP-induced PAC1 receptor signaling and trafficking.
β-Arrestin1 and 2 differentially regulate PACAP-induced PAC1 receptor signaling and trafficking.
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DOI：
10.1371/journal.pone.0196946
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发表时间：
2018
期刊：
影响因子：
3.7
通讯作者：
Hashimoto H
中科院分区：
文献类型：
--
作者：
Shintani Y;Hayata-Takano A;Moriguchi K;Nakazawa T;Ago Y;Kasai A;Seiriki K;Shintani N;Hashimoto H
垂体腺苷酸环化酶激活多肽（PACAP）特异性受体PAC 1 R与多种信号转导途径偶联，包括腺苷酸环化酶、磷脂酶C和细胞外信号调节激酶（ERK）1/2的刺激。PAC 1 R已被证明通过β-arrestin 1和β-arrestin 2发挥其持久和有效的信号。然而，两种β-arrestin亚型在PACAP-PAC 1 R信号传导中的确切作用仍不清楚。我们研究了两种β-arrestin亚型与PAC 1 R之间的相互作用、β-arrestin依赖的PAC 1 R亚细胞定位和ERK 1/2激活。PACAP刺激后，HEK 293 T细胞中PAC 1 R与β-arrestin 1和β-arrestin 2的相互作用相似，但在HeLa细胞和小鼠原代培养的神经元中，PAC 1 R与β-arrestin 2的复合物从细胞表面转移到胞浆中，而β-arrestin 1的复合物则保留在细胞表面区域。沉默β-arrestin 2可阻断PACAP诱导的PAC 1 R内化和ERK 1/2磷酸化，但沉默β-arrestin 1可增加ERK 1/2磷酸化。这些结果表明β-arrestin 1和β-arrestin 2对PAC 1 R内化和PAC 1 R依赖的ERK 1/2激活发挥不同的作用，并表明这两种β-arrestin亚型可能参与PAC 1 R信号通路的精细和精确调节。
A pituitary adenylate cyclase-activating polypeptide (PACAP)-specific receptor, PAC1R, is coupled with multiple signal transduction pathways including stimulation of adenylate cyclase, phospholipase C and extracellular-signal regulated kinase (ERK)1/2. PAC1R has been shown to exert its long-lasting and potent signals via β-arrestin1 and β-arrestin2. However, the precise roles of the two β-arrestin isoforms in PACAP-PAC1R signaling remain unclear. Here we examined the interaction between the two β-arrestin isoforms and PAC1R, β-arrestin-dependent PAC1R subcellular localization and ERK1/2 activation. Upon PACAP stimulation, although PAC1R similarly interacted with β-arrestin1 and β-arrestin2 in HEK293T cells, the complex of PAC1R and β-arrestin2 was translocated from the cell surface into cytosol, but that of β-arrestin1 remained in the cell surface regions in HeLa cells and mouse primary cultured neurons. Silencing of β-arrestin2 blocked PACAP-induced PAC1R internalization and ERK1/2 phosphorylation, but silencing of β-arrestin1 increased ERK1/2 phosphorylation. These results show that β-arrestin1 and β-arrestin2 exert differential actions on PAC1R internalization and PAC1R-dependent ERK1/2 activation, and suggest that the two β-arrestin isoforms may be involved in fine and precise tuning of the PAC1R signaling pathways.
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影响因子：
3.7
作者：
Ogata K;Shintani N;Hayata-Takano A;Kamo T;Higashi S;Seiriki K;Momosaki H;Vaudry D;Vaudry H;Galas L;Kasai A;Nagayasu K;Nakazawa T;Hashimoto R;Ago Y;Matsuda T;Baba A;Hashimoto H
通讯作者：
Hashimoto H
影响因子：
5.6
作者：
Corgiat BA;Nordman JC;Kabbani N
通讯作者：
Kabbani N
影响因子：
4.7
作者：
Gupte RP;Kadunganattil S;Shepherd AJ;Merrill R;Planer W;Bruchas MR;Strack S;Mohapatra DP
通讯作者：
Mohapatra DP
影响因子：
4.8
作者：
Groer, Chad E.;Schmid, Cullen L.;Bohn, Laura M.
通讯作者：
Bohn, Laura M.
影响因子：
15.9
作者：
Freson, K;Hashimoto, H;Van Geet, C
通讯作者：
Van Geet, C