Inhibition of Na+-H+ exchanger-3 interferes with apical receptor-mediated endocytosis via vesicle fusion

Citation
M. Gekle et al., Inhibition of Na+-H+ exchanger-3 interferes with apical receptor-mediated endocytosis via vesicle fusion, J PHYSL LON, 531(3), 2001, pp. 619-629
Citations number
44
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Physiology
Journal title
JOURNAL OF PHYSIOLOGY-LONDON
ISSN journal
0022-3751 → ACNP
Volume
531
Issue
3
Year of publication
2001
Pages
619 - 629
Database
ISI
SICI code
0022-3751(20010315)531:3<619:IONEIW>2.0.ZU;2-0
Abstract
1. Receptor-mediated endocytosis in epithelial cells is a crucial mechanism for transport of macromolecules and regulation of cell-surface protein exp ression. Na+-H+ exchanger type 3 (NHE3) has been shown to cycle between the apical plasma membrane and the early endosomal compartment and to interfer e with endocytosis. 2. In the present study we investigated in detail the NHE3-dependent step o f apical endocytosis in an epithelial cell line (opossum kidney cells). 3. Inhibition of NHE3 led to a rapid dose-dependent inhibition of apical al bumin endocytosis but did not affect basolateral transferrin endocytosis. R e-exocytosis of albumin was not increased by NHE3 inhibition. 4. NHE3 dependency of albumin endocytosis was still observed at 20 degreesC or when microtubules had been disrupted. This was not the case for inhibit ion of vacuolar H+-ATPase. 5. NHE3 inhibition rapidly blocked internalisation of pre-hound albumin and attenuated degradation of internalised albumin without changing general pr otein degradation. 6. Furthermore, NHE3 inhibition reduced the rate of endocytic vesicle fusio n significantly. 7. In summary, our data indicate that NHE3 is important for the early phase of the apical endocytic pathway, located between the plasma membrane and e arly endosomes, at least in part due to its involvement in endocytic vesicl e fusion.