Identification of Sec14‐like 3 as a novel lipid‐packing sensor in the lung

Pulmonary surfactant, a complex composed primarily of lipids and associated proteins, is synthesized in alveolar type II (ATII) cells and secreted into alveoli to prevent collapse during respiration. Although numerous studies have clarified the fundamental roles of pulmonary surfactant, the molecular mechanisms of transport and secretion of pulmonary surfactant remain totally unknown. Thus, we screened candidate genes by comparing genes with the expressed sequence tag (EST) libraries of embryonic and adult lungs by using the digital differential display method in the National Center for Biotechnology Information (NCBI) database. We identified Sec14‐like 3 (Sec14L3) as a new class of lipid‐associated proteins highly expressed in ATII cells. We found that Sec14L3 expression is >100‐fold increased during the perinatal period in the lung. Furthermore, Sec14L3 bound to small‐sized liposomes (30 nm in diameter), but not to large‐sized liposomes (100 nm diameter), through its Sec14 domain. Because of the increased curvature, lipid‐packing defects are more likely to occur in small‐sized liposomes than in large‐sized liposomes. Based on these results, we conclude that Sec14L3 is a new class of lipid‐packing sensor. Sec14L3 may play important roles in the lung, such as intracellular lipid transport, surfactant maturation, and endo/exocytosis.—Hishikawa, D., Shindou, H., Harayama, T., Ogasawara, R., Suwabe, A., Shimizu, T., Identification of Sec14‐like 3 as a novel lipid‐packing sensor in the lung. FASEB J. 27, 5131–5140 (2013). www.fasebj.org