Kv3.3 Channels Bind Hax-1 and Arp2/3 to Assemble a Stable Local Actin Network that Regulates Channel Gating.

Cell 2016 Apr 7

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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 that 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. Copyright © 2016 Elsevier Inc. All rights reserved.

Citation

Yalan Zhang, Xiao-Feng Zhang, Matthew R Fleming, Anahita Amiri, Lynda El-Hassar, Alexei A Surguchev, Callen Hyland, David P Jenkins, Rooma Desai, Maile R Brown, Valeswara-Rao Gazula, Michael F Waters, Charles H Large, Tamas L Horvath, Dhasakumar Navaratnam, Flora M Vaccarino, Paul Forscher, Leonard K Kaczmarek. Kv3.3 Channels Bind Hax-1 and Arp2/3 to Assemble a Stable Local Actin Network that Regulates Channel Gating. Cell. 2016 Apr 7;165(2):434-48