C-terminal domain of ICA69 interacts with PICK1 and acts on trafficking of PICK1-PKCα complex and cerebellar plasticity.
C-terminal domain of ICA69 interacts with PICK1 and acts on trafficking of PICK1-PKCα complex and cerebellar plasticity.
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DOI：
10.1371/journal.pone.0083862
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Shen Y
中科院分区：
文献类型：
--
作者：
Wang Z;Wang YN;Sun CL;Yang D;Su LD;Xie YJ;Zhou L;Wang Y;Shen Y
PICK 1（与C-激酶1相互作用的蛋白质）是一种PKC（蛋白激酶C）结合蛋白，对突触可塑性至关重要。PKCα-PICK 1复合物向质膜的运输对于GluR 2的内化和诱导长期抑制至关重要。ICA 69（胰岛细胞自身抗原69 kDa）被鉴定为PICK 1的主要结合伴侣。虽然异聚体BAR结构域复合物被认为是PICK 1和ICA 69之间相互作用的基础，但ICA 69的C末端结构域（ICAC）在PICK 1-ICA 69复合物中的作用尚不清楚。我们发现ICAC与PICK 1相互作用，调节PICK 1-PKCα复合物的运输。ICAC和ΔICAC（含BAR结构域）可能在ICA 69与PICK 1的结合中发挥不同的作用。ΔICAC结构域呈团簇状分布，ICAC呈弥散分布。ICA 69可抑制活化的PKCα介导的PICK 1向质膜的转运。这种作用可能归因于ICAC，因为ICAC的过表达而不是ΔICAC的过表达阻断了PKCα介导的PICK 1转运。值得注意的是，输注麦芽糖结合蛋白（MBP）融合蛋白，MBP-ICA 69或MBP-ICAC，在小脑浦肯野细胞显着抑制诱导的长期抑郁症在平行纤维和攀爬纤维浦肯野细胞突触。我们的实验表明，ICAC是ICA 69-PICK 1相互作用的重要结构域，并在PICK 1介导的神经元可塑性中起重要作用。
PICK1 (protein interacting with C-kinase 1) is a PKC (protein kinase C)-binding protein, which is essential for synaptic plasticity. The trafficking of PKCα-PICK1 complex to plasma membrane is critical for the internalization of GluR2 and induction of long-term depression. ICA69 (islet cell autoantigen 69 kDa) is identified as a major binding partner of PICK1. While heteromeric BAR domain complex is suggested to underlie the interaction between PICK1 and ICA69, the role of C-terminal domain of ICA69 (ICAC) in PICK1-ICA69 complex is unknown. We found that ICAC interacted with PICK1 and regulated the trafficking of PICK1-PKCα complex. ICAC and ΔICAC (containing BAR domain) might function distinctly in the association of ICA69 with PICK1. While ΔICAC domain inclined to form clusters, the distribution of ICAC was diffuse. The trafficking of PICK1 to plasma membrane mediated by activated PKCα was inhibited by ICA69. This action might ascribe to ICAC, because overexpression of ICAC, but not ΔICAC, interrupted PKCα-mediated PICK1 trafficking. Notably, infusion of maltose binding protein (MBP) fusion protein, MBP-ICA69 or MBP-ICAC, in cerebellar Purkinje cells significantly inhibited the induction of long-term depression at parallel fiber- and climbing fiber-Purkinje cell synapses. Our experiments showed that ICAC is an important domain for the ICA69-PICK1 interaction and plays essential roles in PICK1-mediated neuronal plasticity.
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影响因子：
16.2
作者：
Daw, MI;Chittajallu, R;Isaac, JTR
通讯作者：
Isaac, JTR
影响因子：
4.8
作者：
Quack, Ivo;Woznowski, Magdalena;Sellin, Lorenz
通讯作者：
Sellin, Lorenz
影响因子：
16.2
作者：
Shen, Y;Linden, DJ
通讯作者：
Linden, DJ
DOI：
10.1073/pnas.211132798
发表时间：
2001-09-25
影响因子：
11.1
作者：
Kim, CH;Chung, HJ;Huganir, RL
通讯作者：
Huganir, RL
影响因子：
4.5
作者：
Madsen, Kenneth L.;Eriksen, Jacob;Gether, Ulrik
通讯作者：
Gether, Ulrik