Department of Chemistry and Biochemistry, University of California, Los Angeles, Los Angeles, CA 90095.
Department of Chemistry, Barnard College, New York, NY 10027.
Mol Biol Cell. 2018 Mar 1;29(5):610-621. doi: 10.1091/mbc.E17-06-0363. Epub 2017 Dec 27.
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.
德尔芬林（Delphilin）结合了谷氨酸受体 GluRδ2，存在于浦肯野细胞的树突棘中。这两种蛋白在学习中都起着作用。为了了解德尔芬林在神经元中的功能，我们研究了这种formin 的肌动蛋白聚合特性。formin 具有保守的formin 同源结构域 2，该结构域可以核化并与肌动蛋白丝的快速生长末端结合，与 formin 同源结构域 1（FH1）一起影响丝的生长。成核和延伸的强度在 formin 之间差异很大。此外，大多数 formin 都具有通过分子内相互作用调节肌动蛋白聚合的保守结构域。德尔芬林在几个方面与其他 formin 不同：它的表达仅限于浦肯野细胞，它缺乏经典的自动抑制结构域，并且其 FH1 结构域具有最小的富含脯氨酸序列。我们发现，德尔芬林是一种肌动蛋白成核因子，它不能加速延伸，尽管它可以结合到丝的帽状末端。此外，德尔芬林表现出对肌动蛋白同工型的偏好，能够成核非肌肉肌动蛋白，但不能成核肌肉肌动蛋白，这在其他 formin 中尚未描述或系统地研究过。最后，德尔芬林是第一个研究的不受分子内相互作用调节的 formin。我们推测，我们观察到的活性与其在小的树突棘中的定位是一致的。
