Carbonic anhydrase seven bundles filamentous actin and regulates dendritic spine morphology and density
| Autor: | Mari A. Virtanen, Peter Blaesse, Eva Ruusuvuori, Ville O. Paavilainen, Pirta Hotulainen, Michael Blaesse, Enni Bertling, Laszlo Vutskits, Elena Kremneva, Milla Summanen, Inkeri Spoljaric, Patricia Seja, Kai Kaila, Gergana Gateva, Pavel Uvarov |
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| Přispěvatelé: | Medicum, Neuroscience Center, Molecular and Integrative Biosciences Research Programme, Laboratory of Neurobiology, Institute of Biotechnology, Faculty of Biological and Environmental Sciences, Biosciences, Basal ganglia circuits |
| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
Gene isoform
Dendritic spine actin cytoskeleton Intracellular pH carbonic anhydrase intracellular pH Hippocampus Biochemistry Filamentous actin Article 03 medical and health sciences 0302 clinical medicine Carbonic anhydrase multifunctional protein Genetics Molecular Biology Actin Carbonic Anhydrases 030304 developmental biology Neurons 0303 health sciences biology Chemistry Articles dendritic spines Actin cytoskeleton Actins Cell biology biology.protein 1182 Biochemistry cell and molecular biology Cell Adhesion Polarity & Cytoskeleton 030217 neurology & neurosurgery Intracellular Neuroscience |
| Zdroj: | EMBO Reports |
| Popis: | Intracellular pH is a potent modulator of neuronal functions. By catalyzing (de)hydration of CO2, intracellular carbonic anhydrase (CAi) 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 CO2‐(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. Carbonic anhydrase CA7 is a pH‐regulatory molecule that is expressed in pyramidal neurons at the time of onset of dendritic spinogenesis. This study shows that CA7, but not CA2, binds and bundles actin filaments and has a morphogenetic role in cells. |
| Databáze: | OpenAIRE |
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