| First Author | Wang P | Year | 2007 |
| Journal | Am J Respir Cell Mol Biol | Volume | 37 |
| Issue | 4 | Pages | 467-76 |
| PubMed ID | 17575076 | Mgi Jnum | J:141654 |
| Mgi Id | MGI:3819075 | Doi | 10.1165/rcmb.2006-0447OC |
| Citation | Wang P, et al. (2007) Physical and functional interactions of SNAP-23 with annexin A2. Am J Respir Cell Mol Biol 37(4):467-76 |
| abstractText | Lung surfactant is secreted through the fusion of lamellar bodies with the plasma membrane of alveolar epithelial type II cells. Annexin A2, a Ca(2+)- and phospholipid-binding protein, promotes the fusion of lamellar bodies with the plasma membrane. Soluble N-ethylmaleimide-sensitive factor attachment protein receptors (SNAREs) are known to have an essential role in surfactant secretion. We hypothesized that annexin A2 acts as a Ca(2+) sensor and mediates membrane fusion via its interaction with SNAREs. Both purified or endogenous annexin A2 in type II cells specifically bound with SNAP-23 in a Ca(2+)-dependent manner, as determined by pull-down experiments using recombinant glutathione S-transferase-tagged SNAP-23. A deletion study identified the cysteine-rich region (CRR) of SNAP-23 as the binding site for annexin A2. Mutations of cysteine residues in the CRR dramatically decreased the binding. SNAP-23 also co-immunoprecipitated with annexin A2; however, a SNAP-23 mutant failed to co-immunoprecipitate with annexin A2. Immunofluorescence revealed a co-localization of SNAP-23 and annexin A2 in type II cells. Furthermore, anti-SNAP-23 antibody significantly inhibited annexin A2-mediated fusion between lamellar bodies and the plasma membrane. These data suggest that annexin A2 and SNAP-23 are involved in the same pathway in the regulation of lung surfactant secretion. |
