High impact information on PDR17

• We are only now beginning to appreciate both the identities of PITP-dependent cellular reactions and the intriguing mechanisms by which PITPs execute their functions in eukaryotic cells [1].
• As expected, Sec14pK66,239A fails to meet established criteria for a PITP in vitro and fails to stimulate phosphoinositide production in vivo [2].
• Here, we report the participation of Ssh1p, a soybean PITP-like protein, in the early events of osmosensory signal transduction in plants, a function not attributed previously to animal or yeast PITPs [3].
• The phosphatidylinositol- (PI) loaded form of the yeast PITP, Sec14p, but not the phosphatidylcholine- (PC) loaded form of the protein, was capable of substituting for the cytosolic subfraction in promoting the scission of coated buds from the trans-Golgi network [4].
• A specific anti-PITP antibody that recognizes the two mammalian PITP isoforms fully inhibited the capacity of the cytosol to support normal vesicle generation as well as the uncontrolled vesiculating activity manifested by the cytosolic protein subfraction [4].

Biological context of PDR17

• Collectively, our results indicate that PDR16 and PDR17 control levels of various lipids in various compartments of the cell and thereby provide a mechanism for multidrug resistance unrecognized so far [5].
• The mammalian phosphatidylinositol transfer proteins (PITP) and the yeast Saccharomyces cerevisiae PITP (SEC14p) that show no sequence homology both catalyze exchange of phosphatidylinositol (PI) between membranes compartments in vitro [6].
• The PSTB2 gene was isolated by complementation, and it restores ethanolamine prototrophy and corrects the defective lipid metabolism of the pstB2 strain [7].
• Secondly, all three PITPs were able to rescue phospholipase C-mediated phosphoinositide hydrolysis in PITP-depleted HL60 cells, indicating that all three PITPs were capable of stimulating phosphoinositide synthesis [8].
• Given that the contribution of Sec14p-like proteins to the PITP complement of mammalian cells is completely uninvestigated, and that the mammalian genome encodes many proteins of this class, we anticipate such advances will directly and positively impact our understanding of the molecular basis of such diseases [9].

Anatomical context of PDR17

• We propose that, by delivering PI to specific sites in the Golgi membrane near the necks of coated buds, PITP induces local changes in the organization of the lipid bilayer, possibly involving PI metabolites, that triggers the fusion of the ectoplasmic faces of the Golgi membrane necessary for the scission of COPI-coated vesicles [4].
• These collective findings indicate that the PI 3-kinase and PITP synergize to form a pool of PI 3-phosphate that is essential for formation of exocytic vesicles from the hepatocyte TGN [10].
• In summary, it was shown for the first time that SCP-2 (but not PITP) selectively interacted with caveolin-1, both within the cytoplasm and at the plasma membrane [11].

Associations of PDR17 with chemical compounds

• A new gene involved in the transport-dependent metabolism of phosphatidylserine, PSTB2/PDR17, shares sequence similarity with the gene encoding the phosphatidylinositol/phosphatidylcholine transfer protein, SEC14 [7].
• Deletion of PDR16 had pronounced effects on the sterol composition, whereas PDR17 deletion mainly affected the phospholipid composition [5].
• Both PLCgamma1 and PITP were required to restore inositol lipid signaling [6].
• Increased Sfh4p also significantly reduced the uptake of exogenous Cho [12].
• Overexpression of two Sec14p homologs Sfh2p and Sfh4p in sec14(ts) cells restored secretion and growth at the restrictive temperature but did not restore GPCho accumulation [12].

Other interactions of PDR17

• The C2 (Ca2+ and phospholipid-binding sequence) domain of Psd2p, and the lipid-binding protein PstB2p (PtdSer transport B pathway protein encoded by the PSTB2 gene that complements the pstB2 mutation affecting PtdSer transport), must be present on acceptor membranes for PtdSer transport to occur [13].

References