The neuron-specific formin Delphilin nucleates nonmuscle actin but does not enhance elongation.
The neuron-specific formin Delphilin nucleates nonmuscle actin but does not enhance elongation.
复制标题
神经元特异性形式 Delphilin 使非肌肉肌动蛋白成核，但不增强伸长。
DOI：
10.1091/mbc.e17-06-0363
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发表时间：
2018
影响因子：
3.3
通讯作者：
Vizcarra,ChristinaL
中科院分区：
文献类型：
--
作者：
Silkworth,WilliamT;Kunes,KristinaL;Nickel,GraceC;Phillips,MartinL;Quinlan,MargotE;Vizcarra,ChristinaL
Delphilin结合浦肯野细胞树突棘中的谷氨酸受体GluRδ2。这两种蛋白质都在学习中发挥作用。为了了解Delphilin如何在神经元中发挥作用，我们研究了这种蛋白的肌动蛋白组装特性。形成蛋白有一个保守的肌动蛋白同源性2结构域，它与肌动蛋白丝的快速生长端成核并结合，与肌动蛋白同源性1（FH 1）结构域一起影响肌动蛋白丝的生长。成核和伸长的强度在各种形式之间变化很大。此外，大多数formin具有通过分子内相互作用调节肌动蛋白组装的保守结构域。Delphilin在几个方面与其他formin不同：其表达仅限于浦肯野细胞，缺乏经典的自抑制结构域，其FH 1结构域具有最小的富含脯氨酸的序列。我们发现，Delphilin是一种肌动蛋白成核剂，不加速伸长，但它结合到有倒刺的细丝。此外，Delphilin表现出对肌动蛋白同种型的偏好，使非肌肉肌动蛋白成核而不是肌肉肌动蛋白，这在其他formins中尚未被描述或系统地研究。最后，Delphilin是第一个研究的不受分子内相互作用调节的蛋白质。我们推测我们观察到的活动是如何与其在小树突棘中的定位相一致的。
The formin Delphilin binds the glutamate receptor, GluRδ2, in dendritic spines of Purkinje cells. Both proteins play a role in learning. To understand how Delphilin functions in neurons, we studied the actin assembly properties of this formin. Formins have a conserved formin homology 2 domain, which nucleates and associates with the fast-growing end of actin filaments, influencing filament growth together with the formin homology 1 (FH1) domain. The strength of nucleation and elongation varies widely across formins. Additionally, most formins have conserved domains that regulate actin assembly through an intramolecular interaction. Delphilin is distinct from other formins in several ways: its expression is limited to Purkinje cells, it lacks classical autoinhibitory domains, and its FH1 domain has minimal proline-rich sequence. We found that Delphilin is an actin nucleator that does not accelerate elongation, although it binds to the barbed end of filaments. In addition, Delphilin exhibits a preference for actin isoforms, nucleating nonmuscle actin but not muscle actin, which has not been described or systematically studied in other formins. Finally, Delphilin is the first formin studied that is not regulated by intramolecular interactions. We speculate how the activity we observe is consistent with its localization in the small dendritic spines.