The gene encoding the phosphatidylinositol transfer protein is essential for cell growth.

Aitken, Jacqueline F.; Heusden, G P van; Temkin, M. H.; Dowhan, William

doi:10.1016/s0021-9258(19)39620-6

Cited by 111 publications

(13 citation statements)

References 39 publications

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“…10 and comprise PI, cerarnides, GDP-mannose, and some forms oflPC (IPC~, IPCE). Based on the current knowledge about biosynthesis, intracellular transport and bilayer distribution of PI (Kuchler et ad., 1986;Imai and Gershengorn, 1987;Higgins et al, 1989, Daum et al, 1986Aitken et al, 1990), of ceramides (Bell et al, 1981;Pagano and Sleight, 1985;Lipsky and Pagano, 1985;Futerman et al, 1989) and of GDP-mannose (Abeijon et al, 1989) we presently favor IPC's as the most likely "critical substrateY…”

Section: What Substrate Could Be Transported By Vesicular Flow Only?mentioning

confidence: 95%

Biosynthesis of mannosylinositolphosphoceramide in Saccharomyces cerevisiae is dependent on genes controlling the flow of secretory vesicles from the endoplasmic reticulum to the Golgi.

Puoti

Desponds

Conzelmann

1991

The Journal of Cell Biology

100

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Abstract. Saccharomyces cerevisiae contains several abundant phosphoinositol-containing sphingolipids, namely inositolphosphoceramides (IPCs), mannosylinositolphosphoceramide (MIPC), which is substituted on the headgroup with an additional mannose, and M(IP)2C, a ceramide substituted with one mannose and two phosphoinositol groups. Using well-defined temperature-sensitive secretion mutants we demonstrate that the biosynthesis of MIPC, M(IP)2C, and a subclass if IPCs is dependent on genes that are required for the vesicular transport of proteins from the ER to the Golgi. Synthesis of these lipids in intact cells is dependent on metabolic energy. A likely but tentative interpretation of the data is that the biosynthesis of these sphingolipids is restricted to the Golgi apparatus, and that one or more substrates for the biosynthesis of these sphingolipids (phosphatidylinositol, IPCs, or MIPC) are delivered to the Golgi apparatus by an obligatory vesicular transport step. Alternative models to explain the data are also discussed.

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Section: What Substrate Could Be Transported By Vesicular Flow Only?mentioning

confidence: 95%

Biosynthesis of mannosylinositolphosphoceramide in Saccharomyces cerevisiae is dependent on genes controlling the flow of secretory vesicles from the endoplasmic reticulum to the Golgi.

Puoti

Desponds

Conzelmann

1991

The Journal of Cell Biology

100

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“…E. coli cytosolic preparations (1 mg total protein per reaction) were individually assayed for PI and PC transfer in vitro as previously described (Aitken et al, 1990;Skinner et al, 1993). Sphingomyelin (SM) transfer assays were performed exactly as PC transfer assays, with the exception that [ N -methyl-14 C]SM (56 mCi/mmol; Amersham Corp.) was used as transfer substrate (0.09 Ci per assay).…”

Section: Phospholipid Transfer Assaysmentioning

confidence: 99%

The Phosphatidylinositol Transfer Protein Domain of Drosophila Retinal Degeneration B Protein Is Essential for Photoreceptor Cell Survival and Recovery from Light Stimulation

Milligan

Alb

Elagina

et al. 1997

The Journal of Cell Biology

139

110

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The Drosophila retinal degeneration B (rdgB) gene encodes an integral membrane protein involved in phototransduction and prevention of retinal degeneration. RdgB represents a nonclassical phosphatidylinositol transfer protein (PITP) as all other known PITPs are soluble polypeptides. Our data demonstrate roles for RdgB in proper termination of the phototransduction light response and dark recovery of the photoreceptor cells. Expression of RdgB's PITP domain as a soluble protein (RdgB-PITP) in rdgB2 mutant flies is sufficient to completely restore the wild-type electrophysiological light response and prevent the degeneration. However, introduction of the T59E mutation, which does not affect RdgB-PITP's phosphatidylinositol (PI) and phosphatidycholine (PC) transfer in vitro, into the soluble (RdgB-PITP-T59E) or full-length (RdgB-T59E) proteins eliminated rescue of retinal degeneration in rdgB2 flies, while the light response was partially maintained. Substitution of the rat brain PITPα, a classical PI transfer protein, for RdgB's PITP domain (PITPα or PITPα-RdgB chimeric protein) neither restored the light response nor maintained retinal integrity when expressed in rdgB2 flies. Therefore, the complete repertoire of essential RdgB functions resides in RdgB's PITP domain, but other PITPs possessing PI and/or PC transfer activity in vitro cannot supplant RdgB function in vivo. Expression of either RdgB-T59E or PITPα-RdgB in rdgB + flies produced a dominant retinal degeneration phenotype. Whereas RdgB-T59E functioned in a dominant manner to significantly reduce steady-state levels of rhodopsin, PITPα-RdgB was defective in the ability to recover from prolonged light stimulation and caused photoreceptor degeneration through an unknown mechanism. This in vivo analysis of PITP function in a metazoan system provides further insights into the links between PITP dysfunction and an inherited disease in a higher eukaryote.

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“…Recent reports have suggested a variety of functions for these proteins, including regulation of phospholipid metabolism [9][10][11], facilitation of vesicular traffic and secretion [7,[12][13][14][15][16][17][18][19] and participation in agonist-induced phosphoinositide cycling [20][21][22][23][24][25]. The essential nature of this protein activity for cell survival has been suggested by experiments in both yeast [26] and mammalian cells [27].…”

Section: Introductionmentioning

confidence: 99%

Evidence that mammalian phosphatidylinositol transfer protein regulates phosphatidylcholine metabolism

Monaco

Alexander

Snoek

et al. 1998

Biochemical Journal

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Phosphatidylinositol transfer proteins (PITPs) and their yeast counterpart (SEC14p) possess the ability to bind phosphatidylinositol (PtdIns) and transfer it between membranes in vitro. However, the biochemical function of these proteins in vivo is unclear. In the present study, the physiological role of PITP was investigated by determining the biochemical consequences of lowering the cellular content of this protein. WRK-1 rat mammary tumour cells were transfected with a plasmid containing a full-length rat PITPalpha cDNA inserted in the antisense orientation and the resultant cell clones were analysed. Three clones expressing antisense mRNA for PITPalpha were compared with three clones transfected with the expression vector lacking the insert. The three antisense clones had an average of 25% less PITPalpha protein than control clones. Two of the three antisense clones also exhibited a decreased rate of growth. All three antisense clones exhibited a significant decrease in the incorporation of labelled precursors into PtdCho during a 90-min incubation period. Under the same conditions, however, there was no change in precursor incorporation into PtdIns. Further experimentation indicated that the decrease in precursor incorporation seen in antisense clones was not due to an increased rate of turnover. When choline metabolism was analysed more extensively in one control (2-5) and one antisense (4-B) clone using equilibrium-labelling conditions (48 h of incubation), the following were observed: (1) the decrease in radioactive labelling of PtdCho seen in short-term experiments was also observed in long-term experiments, suggesting that the total amount of PtdCho was lower in antisense-transfected clones (this was confirmed by mass measurements); (2) a similar decrease was seen in cellular sphingomyelin, lysoPtdCho and glycerophosphorylcholine; (3) an average two-fold increase in cellular phosphorylcholine was observed in the antisense-transfected clone; (4) cellular choline was, on average, decreased; and (5) cellular CDPcholine was not significantly altered.

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The gene encoding the phosphatidylinositol transfer protein is essential for cell growth.

Cited by 111 publications

References 39 publications

Biosynthesis of mannosylinositolphosphoceramide in Saccharomyces cerevisiae is dependent on genes controlling the flow of secretory vesicles from the endoplasmic reticulum to the Golgi.

Biosynthesis of mannosylinositolphosphoceramide in Saccharomyces cerevisiae is dependent on genes controlling the flow of secretory vesicles from the endoplasmic reticulum to the Golgi.

The Phosphatidylinositol Transfer Protein Domain of Drosophila Retinal Degeneration B Protein Is Essential for Photoreceptor Cell Survival and Recovery from Light Stimulation

Evidence that mammalian phosphatidylinositol transfer protein regulates phosphatidylcholine metabolism

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