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J. Biol. Chem., Vol. 283, Issue 19, 13156-13164, May 9, 2008

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Annexin A2 Interactions with Rab14 in Alveolar Type II Cells^*

From the Department of Physiological Sciences, Oklahoma State University, Stillwater, Oklahoma 74078

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.

Received for publication, February 25, 2008 , and in revised form, March 10, 2008.

^* This work was supported, in whole or in part, by National Institutes of Health Grants R01 HL-052146, R01 HL-071628, and R01 HL-083188 (to L. L.). This work was also supported by a Center for Veterinary Health Sciences seed grant (to D. G.). The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

¹ To whom correspondence should be addressed: Dept. of Physiological Sciences, Oklahoma State University, 264 McElroy Hall, Stillwater, OK 74078. Tel.: 405-744-4526; Fax: 405-744-8263; E-mail: lin.liu{at}okstate.edu.

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