Abstract
Annexin A2, a calcium-dependent phospholipid-binding protein, is abundantly expressed in alveolar type II cells where it plays a role in lung surfactant secretion. Nevertheless, little is known about the details of its cellular pathways. To identify annexin A2-regulated or associated proteins, we silenced endogenous annexin A2 expression in rat alveolar type II cells by RNA interference and assessed the change of the cellular transcriptome by DNA microarray analysis. The loss of annexin A2 resulted in the change of 61 genes. Thirteen of the selected genes (11 down-regulated and 2 up-regulated genes) were validated by real time quantitative PCR. When the loss of rat annexin A2 was rescued by overexpressing EGFP-tagged human annexin A2, six of seven selected targets returned to their normal expression level, indicating that these genes are indeed annexin A2-associated targets. One of the targets, Rab14, co-immunoprecipitated with annexin A2. Rab14 also co-localized in part with annexin A2 and lamellar bodies in alveolar type II cells. The silencing of Rab14 resulted in a decrease in surfactant secretion, suggesting that Rab14 may play a role in surfactant secretion.
Highlights
The alveolar epithelium is composed of morphologically and functionally distinct type I and II cells
At an m.o.i. of 50, a time course analysis that tested the effects of the adenovirus at 24, 48, and 72 h showed that the amount of annexin A2 protein was reduced by Ͼ98% 72 h after transduc
Annexins are multifunctional proteins involved in diverse cellular processes such as the control of intracellular calcium, vesicle trafficking, exocytosis and inhibition of phospholipase A2 and blood coagulation [6, 7]
Summary
The alveolar epithelium is composed of morphologically and functionally distinct type I and II cells. Lung surfactant is stored and secreted by exocytosis of lamellar bodies, which are specialized organelles found in type II cells. In alveolar type II cells, accumulating evidence supports a role for annexin A2 in controlling the fusion of lamellar bodies with the plasma membrane and promoting surfactant secretion [11,12,13,14]. The expression of annexin A2 in rat type II cells was silenced by adenovirus-mediated short hairpin RNA (shRNA) to identify annexin A2-related genes at a genomic level. Of great interest is Rab, which physically interacts with annexin A2 and is functionally related to annexin A2-mediated surfactant secretion This finding provides another piece to the puzzle of the mechanisms of lung surfactant secretion and will help guide future experiments in this field of research
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