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Remodeling neuronal ER-PM junctions is a conserved nonconducting function of Kv2 plasma membrane ion channels.

Molecular biology of the cell | 2018

The endoplasmic reticulum (ER) and plasma membrane (PM) form junctions crucial to ion and lipid signaling and homeostasis. The Kv2.1 ion channel is localized at ER-PM junctions in brain neurons and is unique among PM proteins in its ability to remodel these specialized membrane contact sites. Here, we show that this function is conserved between Kv2.1 and Kv2.2, which differ in their biophysical properties, modulation, and cellular expression. Kv2.2 ER-PM junctions are present at sites deficient in the actin cytoskeleton, and disruption of the actin cytoskeleton affects their spatial organization. Kv2.2-containing ER-PM junctions overlap with those formed by canonical ER-PM tethers. The ability of Kv2 channels to remodel ER-PM junctions is unchanged by point mutations that eliminate their ion conduction but eliminated by point mutations within the Kv2-specific proximal restriction and clustering (PRC) domain that do not impact their ion channel function. The highly conserved PRC domain is sufficient to transfer the ER-PM junction-remodeling function to another PM protein. Last, brain neurons in Kv2 double-knockout mice have altered ER-PM junctions. Together, these findings demonstrate a conserved in vivo function for Kv2 family members in remodeling neuronal ER-PM junctions that is distinct from their canonical role as ion-conducting channels shaping neuronal excitability.

Pubmed ID: 30091655 RIS Download

Research resources used in this publication

Associated grants

  • Agency: NINDS NIH HHS, United States
    Id: R01 NS042225
  • Agency: NINDS NIH HHS, United States
    Id: R01 NS096317
  • Agency: NIGMS NIH HHS, United States
    Id: T32 GM007377
  • Agency: NINDS NIH HHS, United States
    Id: U01 NS090581

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