LINGO1 is a regulatory subunit of large conductance, Ca2+-activated potassium channels

Proc Natl Acad Sci U S A. 2020 Jan 28;117(4):2194-2200. doi: 10.1073/pnas.1916715117. Epub 2020 Jan 13.


LINGO1 is a transmembrane protein that is up-regulated in the cerebellum of patients with Parkinson's disease (PD) and Essential Tremor (ET). Patients with additional copies of the LINGO1 gene also present with tremor. Pharmacological or genetic ablation of large conductance Ca2+-activated K+ (BK) channels also result in tremor and motor disorders. We hypothesized that LINGO1 is a regulatory BK channel subunit. We show that 1) LINGO1 coimmunoprecipitated with BK channels in human brain, 2) coexpression of LINGO1 and BK channels resulted in rapidly inactivating BK currents, and 3) LINGO1 reduced the membrane surface expression of BK channels. These results suggest that LINGO1 is a regulator of BK channels, which causes a "functional knockdown" of these currents and may contribute to the tremor associated with increased LINGO1 levels.

Keywords: BK channels; LINGO1; Parkinson’s disease; accessory subunits; leucine-rich repeat containing proteins.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Cell Line
  • Cerebellum / metabolism
  • Humans
  • Large-Conductance Calcium-Activated Potassium Channels / genetics
  • Large-Conductance Calcium-Activated Potassium Channels / metabolism*
  • Membrane Proteins / genetics
  • Membrane Proteins / metabolism*
  • Nerve Tissue Proteins / genetics
  • Nerve Tissue Proteins / metabolism*
  • Protein Binding


  • LINGO1 protein, human
  • Large-Conductance Calcium-Activated Potassium Channels
  • Membrane Proteins
  • Nerve Tissue Proteins