Journal
JOURNAL OF CELL SCIENCE
Volume 128, Issue 11, Pages 2096-2105Publisher
COMPANY BIOLOGISTS LTD
DOI: 10.1242/jcs.166009
Keywords
Ion channels; Sub-surface cisterns; Membrane contact sites
Categories
Funding
- National Institutes of Health [R01GM84136, R01GM084136S1, RO1GM109888]
- National Science Foundation [1401432]
- Division Of Physics
- Direct For Mathematical & Physical Scien [1401432] Funding Source: National Science Foundation
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Junctions between cortical endoplasmic reticulum (cER) and the plasma membrane are a subtle but ubiquitous feature in mammalian cells; however, very little is known about the functions and molecular interactions that are associated with neuronal ER-plasma-membrane junctions. Here, we report that Kv2.1 (also known as KCNB1), the primary delayed-rectifier K+ channel in the mammalian brain, induces the formation of ER-plasma-membrane junctions. Kv2.1 localizes to dense, cell-surface clusters that contain non-conducting channels, indicating that they have a function that is unrelated to membrane-potential regulation. Accordingly, Kv2.1 clusters function as membrane-trafficking hubs, providing platforms for delivery and retrieval of multiple membrane proteins. Using both total internal reflection fluorescence and electron microscopy we demonstrate that the clustered Kv2.1 plays a direct structural role in the induction of stable ER-plasma-membrane junctions in both transfected HEK 293 cells and cultured hippocampal neurons. Glutamate exposure results in a loss of Kv2.1 clusters in neurons and subsequent retraction of the cER from the plasma membrane. We propose Kv2.1-induced ER-plasma-membrane junctions represent a new macromolecular plasma-membrane complex that is sensitive to excitotoxic insult and functions as a scaffolding site for both membrane trafficking and Ca2+ signaling.
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