Long phospholipid transfer proteins (PLTPs) are useful tools for studying the distribution of surfactant phospholipids in lung subcellular organelles. PLTPs in lung might be involved in: (1) intracellular transfer of surfactant phospholipids from endoplasmic reticulum synthetic site to the lamellar body storage site; (2) selective sorting of surfactant phospholipids in lamellar bodies; and (3) recycling of surfactant phospholipids between the alveolar surface and lamellar bodies. Recently three PLTPs have been purified from adult rabbit lungs in the investigator's laboratory. Preliminary data shows that the three PLTPs are all able to transfer phosphatidylcholine (PC), but have diverse properties with respect to substrate specificity, effects of membrane charge, hydrophobicity, isoelectric points, molecular weights and response to Ca2+ effect on membrane fusion. Therefore, the objective of this proposed research is to study the structure, function and regulation of these PLTPs.
The specific aims of this proposed research are: (1) to study the developmental regulation of the three PLTPs and to elucidate the relationships between PLTPs and lung maturation; (2) to study the structural characteristics of these three PLTPs to help understand their structure-function relationships; and (3) to use a monolayer method to study the transfer of these three PLTPs and to use this technique as a model to probe the recycling of phospholipids. A comparative study of the three PLTPs is important for understanding of the roles of PLTPs in the processes of transfer, sorting and recycling of surfactant phospholipids. The results of this proposed study will shed light on the clinically important disease of neonatal respiratory distress syndrome which is primarily caused by a deficiency of surfactant due to a delay in synthesis, transfer or secretion.
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