| First Author | Lee HJ | Year | 2024 |
| Journal | Sci Adv | Volume | 10 |
| Issue | 41 | Pages | eadm8663 |
| PubMed ID | 39383236 | Mgi Jnum | J:359556 |
| Mgi Id | MGI:7787186 | Doi | 10.1126/sciadv.adm8663 |
| Citation | Lee HJ, et al. (2024) SLC26A4-AP-2 mu2 interaction regulates SLC26A4 plasma membrane abundance in the endolymphatic sac. Sci Adv 10(41):eadm8663 |
| abstractText | 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 mu2 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 mu2 and AP-2 are present. Based on SLC26A4 structure, the elements involved in SLC26A4-mu2 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-mu2 interaction regulates SLC26A4 abundance at the apical surface of mitochondria-rich cells. |
