SLC26A4-AP-2 mu2 interaction regulates SLC26A4 plasma membrane abundance in the endolymphatic sac.
Sci Adv
; 10(41): eadm8663, 2024 Oct 11.
Article
in En
| MEDLINE
| ID: mdl-39383236
ABSTRACT
Decreased presence or activity of human SLC26A4 at the plasma membrane is a common cause of hearing loss. SLC26A4 (Pendrin) is necessary for normal reabsorption of endolymph, the fluid bathing the inner ear. We identified the µ2 subunit of adaptor protein 2 (AP-2) complex required for clathrin-mediated endocytosis as a protein-partner of SLC26A4 involved in regulating its plasma membrane abundance. We showed that, in the endolymphatic sac, where fluid reabsorption occurs, SLC26A4 is localized along the apical microvilli of mitochondria-rich cells, in contact with the endolymph, and associated with clathrin-coated pits where µ2 and AP-2 are present. Based on SLC26A4 structure, the elements involved in SLC26A4-µ2 interaction were identified and validated experimentally, allowing modeling of this interaction at the atomic level. Pharmacological inhibition of clathrin-mediated endocytosis led to an increased plasma membrane abundance of hemagglutinin-tagged SLC26A4 virally or endogenously expressed in mitochondria-rich cells. These results indicate that the SLC26A4-µ2 interaction regulates SLC26A4 abundance at the apical surface of mitochondria-rich cells.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Cell Membrane
/
Endolymphatic Sac
/
Adaptor Protein Complex 2
/
Endocytosis
/
Sulfate Transporters
Limits:
Animals
/
Humans
Language:
En
Journal:
Sci Adv
/
Sci. Adv
/
Science advances
Year:
2024
Document type:
Article
Affiliation country:
United States
Country of publication:
United States