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

Abstract

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.

Sphingolipid transfer proteins defined by the GLTP-fold

“…Nonenzymic proteins capable of binding lipids exist for a variety of different purposes within cells, as evidenced by a host of recent publications (Blind et al 2014; De Libero & Mori, 2012; Drin, 2014; Garzón et al 2013; Hashikawa et al 2013; Holthuis & Menon, 2014; Kono et al 2013; Luoma et al 2014; Maceyka & Spiegel, 2014; Maeda et al 2013; Mesmin et al 2013; Olkkonen & Li, 2013; Ren et al 2014; Roulin et al 2014; Sandhoff & Harzer, 2013; Schulze & Sandhoff, 2014). The purposes include: (i) presentation of lipids to hydrolytic proteins for degradation and salvage of breakdown products to rebuild and recycle needed lipid components; (ii) presentation of lipids to proteins of the immune system during development of antigenicity; (iii) sensing of intracellular lipid compositions in membranes of various organelles; and (iv) transfer of lipids between intracellular membranes of different organelles.…”

Pulmonary microRNA profiles identify involvement of Creb1 and Sec14l3 in bronchial epithelial changes in allergic asthma

“…Nonetheless, the CRE-element in the Sec14l3 promoter is evolutionary highly conserved, suggesting functional relevance. Little is known regarding functions of Sec14l3, which is highly induced around birth in lung tissue51. In mammalians more than 20 Sec14 family members have been described, carrying highly conserved lipid-binding domains52.…”

“…In mammalians more than 20 Sec14 family members have been described, carrying highly conserved lipid-binding domains52. Sec14l3 has been specifically implicated in the intracellular transport of α-tocopherol53 and has been proposed as sensor of liposomal lipid-packing defects in the lung51. Human SEC14L3 has been found to be decreased in bronchial and nasal epithelium of smokers54 and during human rhinovirus infection55.…”

Lysophosphatidylcholine Acyltransferase 1 (LPCAT1) Specifically Interacts with Phospholipid Transfer Protein StarD10 to Facilitate Surfactant Phospholipid Trafficking in Alveolar Type II Cells

“…Most recently, Hishikawa et al (68) have identified Sec14L3 as a phospholipid transporter in alveolar type II cells. Sec14L3, a Sec14 homolog, not only has an expression pattern similar to LPCAT1 and StarD10 but also binds to a variety of PC species.…”