Actin'g against the Ball and Chain
| Autor: | Jasmine V. Abella, Michael Way |
|---|---|
| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Shaw Potassium Channels Cell Biology macromolecular substances Spinocerebellar Degenerations Biology medicine.disease General Biochemistry Genetics and Molecular Biology Potassium channel Actins Article Cell biology 03 medical and health sciences 030104 developmental biology Biochemistry Polymerization Mutation medicine Humans Molecular Biology Actin Developmental Biology Spinocerebellar ataxia type-13 |
| Zdroj: | Developmental cell. 37(1) |
| ISSN: | 1878-1551 |
| Popis: | Mutations in the Kv3.3 potassium channel (KCNC3) cause cerebellar neurodegeneration and impair auditory processing. The cytoplasmic C-terminus of Kv3.3 contains a proline-rich domain conserved in proteins that activate actin nucleation through Arp2/3. We found that Kv3.3 recruits Arp2/3 to the plasma membrane, resulting in formation of a relatively stable cortical actin filament network resistant to cytochalasin D which inhibits fast barbed end actin assembly. These Kv3.3-associated actin structures are required to prevent very rapid N-type channel inactivation during short depolarizations of the plasma membrane. The effects of Kv3.3 on the actin cytoskeleton are mediated by the binding of the cytoplasmic C-terminus of Kv3.3 to Hax-1, an anti-apoptotic protein that regulates actin nucleation through Arp2/3. A human Kv3.3 mutation within a conserved proline-rich domain produces channels that bind Hax-1 but are impaired in recruiting Arp2/3 to the plasma membrane, resulting in growth cones with deficient actin veils in stem cell-derived neurons. |
| Databáze: | OpenAIRE |
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