Mimicking Protein Kinase C Phosphorylation Inhibits Arc/Arg3.1 Palmitoylation and Its Interaction with Nucleic Acids.
Mimicking Protein Kinase C Phosphorylation Inhibits Arc/Arg3.1 Palmitoylation and Its Interaction with Nucleic Acids.
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DOI：
10.3390/ijms25020780
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发表时间：
2024-01-08
影响因子：
5.6
通讯作者：
中科院分区：
文献类型：
--
作者：
活动调节的细胞因子相关蛋白（Activity-regulated cytokeron-associated protein，Arc）在突触可塑性的多种形式中发挥重要作用，包括长时程增强（long-term potentiation，LTP）、长时程抑制（long-term depression，LTD）和稳态可塑性。此外，它组装成病毒样颗粒，可以在神经元和相邻细胞之间传递mRNA和/或其他货物。考虑到这种广泛的活性，Arc受到多种类型的翻译后修饰的调节并不奇怪，包括磷酸化、棕榈酰化、SUMO化、泛素化和乙酰化。在这里，我们探讨了蛋白激酶C（PKC）对Arc磷酸化的潜在调节作用，PKC发生在N端结构域α螺旋片段内的丝氨酸84和90上。为了模拟PKC磷酸化的作用，我们将两种丝氨酸突变为带负电荷的谷氨酸。引入这些拟磷酸突变的结果是几乎完全抑制了Arc棕榈酰化，其发生在附近的半胱氨酸上并有助于突触弱化。突变还抑制核酸的结合并使高阶Arc寡聚体不稳定。因此，PKC磷酸化的Arc可能会限制LTD的充分表达，并可能抑制mRNA的神经元间的运输。
Activity-regulated cytoskeleton-associated protein (Arc) plays essential roles in diverse forms of synaptic plasticity, including long-term potentiation (LTP), long-term depression (LTD), and homeostatic plasticity. In addition, it assembles into virus-like particles that may deliver mRNAs and/or other cargo between neurons and neighboring cells. Considering this broad range of activities, it is not surprising that Arc is subject to regulation by multiple types of post-translational modification, including phosphorylation, palmitoylation, SUMOylation, ubiquitylation, and acetylation. Here we explore the potential regulatory role of Arc phosphorylation by protein kinase C (PKC), which occurs on serines 84 and 90 within an α-helical segment in the N-terminal domain. To mimic the effect of PKC phosphorylation, we mutated the two serines to negatively charged glutamic acid. A consequence of introducing these phosphomimetic mutations is the almost complete inhibition of Arc palmitoylation, which occurs on nearby cysteines and contributes to synaptic weakening. The mutations also inhibit the binding of nucleic acids and destabilize high-order Arc oligomers. Thus, PKC phosphorylation of Arc may limit the full expression of LTD and may suppress the interneuronal transport of mRNAs.
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影响因子：
4.7
作者：
通讯作者：
--
影响因子：
15.9
作者：
Korb E;Finkbeiner S
通讯作者：
Finkbeiner S
影响因子：
64.5
作者：
Ashley J;Cordy B;Lucia D;Fradkin LG;Budnik V;Thomson T
通讯作者：
Thomson T
影响因子：
64.8
作者：
Jumper J;Evans R;Pritzel A;Green T;Figurnov M;Ronneberger O;Tunyasuvunakool K;Bates R;Žídek A;Potapenko A;Bridgland A;Meyer C;Kohl SAA;Ballard AJ;Cowie A;Romera-Paredes B;Nikolov S;Jain R;Adler J;Back T;Petersen S;Reiman D;Clancy E;Zielinski M;Steinegger M;Pacholska M;Berghammer T;Bodenstein S;Silver D;Vinyals O;Senior AW;Kavukcuoglu K;Kohli P;Hassabis D
通讯作者：
Hassabis D
影响因子：
2.9
作者：
Barylko, Barbara;Wilkerson, Julia R.;Cavalier, Sheridan H.;Binns, Derk D.;James, Nicholas G.;Jameson, David M.;Huber, Kimberly M.;Albanesi, Joseph P.
通讯作者：
Albanesi, Joseph P.