LINGO1 is a regulatory subunit of large conductance, Ca2+-activated potassium channels.
Proc Natl Acad Sci U S A
; 117(4): 2194-2200, 2020 01 28.
Article
in En
| MEDLINE
| ID: mdl-31932443
ABSTRACT
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.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Large-Conductance Calcium-Activated Potassium Channels
/
Membrane Proteins
/
Nerve Tissue Proteins
Limits:
Humans
Language:
En
Journal:
Proc Natl Acad Sci U S A
Year:
2020
Document type:
Article
Affiliation country:
Ireland