Mice without phosphatidylcholine transfer protein have no defects in the secretion of phosphatidylcholine into bile or into lung airspaces

Abstract

Phosphatidylcholine transfer protein (Pc-tp) is a highly specific carrier of phosphatidylcholine (PC) without known function. Proposed functions include the supply of PC required for secretion into bile or lung air space (surfactant) and the facilitation of enzymatic reactions involving PC synthesis or breakdown. To test these functions, we generated knock-out mice unable to make Pc-tp. Remarkably, these mice are normal and have no defect in any of the postulated Pc-tp functions analyzed. The lipid content and composition of the bile, as well as lung surfactant secretion and composition, of Pc-tp (؊͞؊) mice, is normal. The lack of a Pc-tp contribution to biliary lipid secretion is in agreement with our finding that Pc-tp is down-regulated in adult mouse liver: whereas Pc-tp is abundant in the liver of mouse pups, Pc-tp levels decrease > 10-fold around 2 wk after birth, when bile formation starts. In adult mice, Pc-tp levels are high only in epididymis, testis, kidney, and bone marrow-derived mast cells. Absence of Pc-tp in bone marrow-derived mast cells does not affect their lipid composition or PC synthesis and degradation. We discuss how PC might reach the canalicular membrane of the hepatocyte for secretion into the bile, if not by Pc-tp.

Interacting Proteins Dictate Function of the Minimal START Domain Phosphatidylcholine Transfer Protein/StarD2

“…2A, hybridization using a multiple tissue Northern blot revealed substantial expression of Them2 mRNA in heart, brain, liver, kidney, and skeletal muscle, in general agreement with recent observations by reverse transcription-PCR in human tissues (26). As confirmed here, PC-TP is expressed in mouse liver as well as other tissues (27). To explore whether enrichment of Them2 in liver was due principally to its expression in hepatocytes, we carried out quantitative real time PCR using pertinent available individual cell types (Fig.…”

“…An important limitation of this experiment is that it did not include other coactivators that up-regulate activity of Pax3, including Sox10 (16). Unlike mutations in Pax3 (39), Pctp Ϫ/Ϫ mice do not develop gross cardiac abnormalities (27). Whether the absence of PC-TP leads to more subtle cardiac or neural malformations has yet to be elucidated.…”

“…2A and Ref. 26) that overlaps with PC-TP (9,27). Recently, a GFP-hThem2 construct was localized to microtubules in a U2OS osteosarcoma cell line (26).…”

Targeted Mutation of the MLN64 START Domain Causes Only Modest Alterations in Cellular Sterol Metabolism

“…Having said this, we cannot rule out the possibility that a dietary manipulation not explored in our experiments might bring out a more profound alteration in lipid metabolism in the nullizygous mice. It should be noted that targeted mutation in another START domain protein, phosphatidylcholine transfer protein (StarD2), did not result in a demonstrable hepatic phenotype in phospholipid metabolism (37). Alternatively, it may be that the MLN64 N-terminal domain, which is retained in our mutants, plays an unexpected role in sterol trafficking.…”

The mammalian START domain protein family in lipid transport in health and disease

“…The initial proposed functions for PCTP were in PC transport across the hepatic canalicular membrane and for lung surfactant synthesis, given that PC is the major phospholipid in bile and surfactant and the transporter is expressed in the hepatocytes and alveolar cells (van Helvoort et al 1999). However, PCTP knockout mice (Pctp…”