Neuroscience Center, HiLIFE, University of Helsinki, Helsinki, Finland.
Minerva Institute for Medical Research, Biomedicum Helsinki 2U, Helsinki, Finland.
EMBO Rep. 2021 Apr 7;22(4):e50145. doi: 10.15252/embr.202050145. Epub 2021 Mar 15.
Intracellular pH is a potent modulator of neuronal functions. By catalyzing (de)hydration of CO , intracellular carbonic anhydrase (CA ) isoforms CA2 and CA7 contribute to neuronal pH buffering and dynamics. The presence of two highly active isoforms in neurons suggests that they may serve isozyme-specific functions unrelated to CO -(de)hydration. Here, we show that CA7, unlike CA2, binds to filamentous actin, and its overexpression induces formation of thick actin bundles and membrane protrusions in fibroblasts. In CA7-overexpressing neurons, CA7 is enriched in dendritic spines, which leads to aberrant spine morphology. We identified amino acids unique to CA7 that are required for direct actin interactions, promoting actin filament bundling and spine targeting. Disruption of CA7 expression in neocortical neurons leads to higher spine density due to increased proportion of small spines. Thus, our work demonstrates highly distinct subcellular expression patterns of CA7 and CA2, and a novel, structural role of CA7.
细胞内 pH 值是神经元功能的一个有力调节剂。通过催化 CO 的（去）水合作用，细胞内碳酸酐酶（CA）同工型 CA2 和 CA7 有助于神经元的 pH 值缓冲和动态变化。神经元中存在两种高活性同工型表明它们可能具有与 CO 的（去）水合作用无关的同工酶特异性功能。在这里，我们表明 CA7 与 CA2 不同，它可以与丝状肌动蛋白结合，并且其过表达可诱导成纤维细胞中形成厚的肌动蛋白束和膜突起。在 CA7 过表达的神经元中，CA7 在树突棘中富集，导致异常的棘突形态。我们确定了 CA7 特有的氨基酸，这些氨基酸对于直接与肌动蛋白相互作用、促进肌动蛋白丝束集和棘突靶向是必需的。破坏新皮质神经元中的 CA7 表达会由于小棘突比例增加而导致棘突密度增加。因此，我们的工作表明 CA7 和 CA2 具有高度不同的细胞内表达模式，以及 CA7 的一种新的结构作用。
