|
|
|
|
A more recent version of this article appeared on September 1, 2002
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Submitted on March 28, 2002
Revised on May 23, 2002
Accepted on June 5, 2002
1 Department of Biological Sciences, Vanderbilt University, Nashville, TN 37235-1634
* Corresponding author. E-mail address: tr.graham{at}vanderbilt.edu.
The Saccharomyces cerevisiae genome contains five genes encoding P-type ATPases that are potential aminophospholipid translocases (APTs); DRS2, NEO1, and three uncharacterized ORFs, which we have named DNF1, DNF2 and DNF3 for DRS2/NEO1 Family. NEO1 is the only essential gene in APT family and appears to be functionally distinct from the DRS2/DNF genes. The drs2
dnf1
dnf2
dnf3
quadruple mutant is inviable although any one member of this group can maintain viability, indicating that there is a substantial functional overlap between the encoded proteins. We have previously implicated Drs2p in clathrin function at the trans-Golgi network (TGN). In this study, we constructed strains carrying all possible viable combinations of null alleles from this group and analyzed them for defects in protein transport. The drs2
dnf1
mutant grows slowly, massively accumulates intracellular membranes, and exhibits a substantial defect in the transport of alkaline phosphatase (ALP) to the vacuole. Transport of carboxypeptidase Y (CPY) to the vacuole is also perturbed, but to a lesser extent. In addition, the dnf1
dnf2
dnf3
mutant exhibits a defect in recycling of GFP-Snc1p in the early endocytic - late secretory pathways. Drs2p and Dnf3p colocalize with the TGN marker Kex2p, while Dnf1p and Dnf2p appear to localize to the plasma membrane and late exocytic or early endocytic membranes. We propose that eukaryotes express multiple APT subfamily members to facilitate protein transport in multiple pathways.
This article has been cited by other articles:
![]() |
K. Liu, K. Surendhran, S. F. Nothwehr, and T. R. Graham P4-ATPase Requirement for AP-1/Clathrin Function in Protein Transport from the trans-Golgi Network and Early Endosomes Mol. Biol. Cell, August 1, 2008; 19(8): 3526 - 3535. [Abstract] [Full Text] [PDF] |
||||
![]() |
M. Ikeda, A. Kihara, A. Denpoh, and Y. Igarashi The Rim101 Pathway Is Involved in Rsb1 Expression Induced by Altered Lipid Asymmetry Mol. Biol. Cell, May 1, 2008; 19(5): 1922 - 1931. [Abstract] [Full Text] [PDF] |
||||
![]() |
K. Nakano, T. Yamamoto, T. Kishimoto, T. Noji, and K. Tanaka Protein Kinases Fpk1p and Fpk2p are Novel Regulators of Phospholipid Asymmetry Mol. Biol. Cell, April 1, 2008; 19(4): 1783 - 1797. [Abstract] [Full Text] [PDF] |
||||
![]() |
L. R. Poulsen, R. L. Lopez-Marques, S. C. McDowell, J. Okkeri, D. Licht, A. Schulz, T. Pomorski, J. F. Harper, and M. G. Palmgren The Arabidopsis P4-ATPase ALA3 Localizes to the Golgi and Requires a {beta}-Subunit to Function in Lipid Translocation and Secretory Vesicle Formation PLANT CELL, March 1, 2008; 20(3): 658 - 676. [Abstract] [Full Text] [PDF] |
||||
![]() |
T. Szul, R. Grabski, S. Lyons, Y. Morohashi, S. Shestopal, M. Lowe, and E. Sztul Dissecting the role of the ARF guanine nucleotide exchange factor GBF1 in Golgi biogenesis and protein trafficking J. Cell Sci., November 15, 2007; 120(22): 3929 - 3940. [Abstract] [Full Text] [PDF] |
||||
![]() |
L. K. Schroeder, S. Kremer, M. J. Kramer, E. Currie, E. Kwan, J. L. Watts, A. L. Lawrenson, and G. J. Hermann Function of the Caenorhabditis elegans ABC Transporter PGP-2 in the Biogenesis of a Lysosome-related Fat Storage Organelle Mol. Biol. Cell, March 1, 2007; 18(3): 995 - 1008. [Abstract] [Full Text] [PDF] |
||||
![]() |
K. Liu, Z. Hua, J. A. Nepute, and T. R. Graham Yeast P4-ATPases Drs2p and Dnf1p Are Essential Cargos of the NPFXD/Sla1p Endocytic Pathway Mol. Biol. Cell, February 1, 2007; 18(2): 487 - 500. [Abstract] [Full Text] [PDF] |
||||
![]() |
D. L. Daleke Phospholipid Flippases J. Biol. Chem., January 12, 2007; 282(2): 821 - 825. [Full Text] [PDF] |
||||
![]() |
N. Furuta, K. Fujimura-Kamada, K. Saito, T. Yamamoto, and K. Tanaka Endocytic Recycling in Yeast Is Regulated by Putative Phospholipid Translocases and the Ypt31p/32p-Rcy1p Pathway Mol. Biol. Cell, January 1, 2007; 18(1): 295 - 312. [Abstract] [Full Text] [PDF] |
||||
![]() |
N. Alder-Baerens, Q. Lisman, L. Luong, T. Pomorski, and J. C.M. Holthuis Loss of P4 ATPases Drs2p and Dnf3p Disrupts Aminophospholipid Transport and Asymmetry in Yeast Post-Golgi Secretory Vesicles Mol. Biol. Cell, April 1, 2006; 17(4): 1632 - 1642. [Abstract] [Full Text] [PDF] |
||||
![]() |
T. Kishimoto, T. Yamamoto, and K. Tanaka Defects in Structural Integrity of Ergosterol and the Cdc50p-Drs2p Putative Phospholipid Translocase Cause Accumulation of Endocytic Membranes, onto Which Actin Patches Are Assembled in Yeast Mol. Biol. Cell, December 1, 2005; 16(12): 5592 - 5609. [Abstract] [Full Text] [PDF] |
||||
![]() |
S W C van Mil, R H J Houwen, and L W J Klomp Genetics of familial intrahepatic cholestasis syndromes J. Med. Genet., June 1, 2005; 42(6): 449 - 463. [Abstract] [Full Text] [PDF] |
||||
![]() |
A. Kihara and Y. Igarashi Cross Talk between Sphingolipids and Glycerophospholipids in the Establishment of Plasma Membrane Asymmetry Mol. Biol. Cell, November 1, 2004; 15(11): 4949 - 4959. [Abstract] [Full Text] [PDF] |
||||
![]() |
S. Wicky, H. Schwarz, and B. Singer-Kruger Molecular Interactions of Yeast Neo1p, an Essential Member of the Drs2 Family of Aminophospholipid Translocases, and Its Role in Membrane Trafficking within the Endomembrane System Mol. Cell. Biol., September 1, 2004; 24(17): 7402 - 7418. [Abstract] [Full Text] [PDF] |
||||
![]() |
A. Bugnicourt, M. Froissard, K. Sereti, H. D. Ulrich, R. Haguenauer-Tsapis, and J.-M. Galan Antagonistic Roles of ESCRT and Vps Class C/HOPS Complexes in the Recycling of Yeast Membrane Proteins Mol. Biol. Cell, September 1, 2004; 15(9): 4203 - 4214. [Abstract] [Full Text] [PDF] |
||||
![]() |
P. Natarajan, J. Wang, Z. Hua, and T. R. Graham Drs2p-coupled aminophospholipid translocase activity in yeast Golgi membranes and relationship to in vivo function PNAS, July 20, 2004; 101(29): 10614 - 10619. [Abstract] [Full Text] [PDF] |
||||
![]() |
K. Saito, K. Fujimura-Kamada, N. Furuta, U. Kato, M. Umeda, and K. Tanaka Cdc50p, a Protein Required for Polarized Growth, Associates with the Drs2p P-Type ATPase Implicated in Phospholipid Translocation in Saccharomyces cerevisiae Mol. Biol. Cell, July 1, 2004; 15(7): 3418 - 3432. [Abstract] [Full Text] [PDF] |
||||
![]() |
T. Pomorski, J. C. M. Holthuis, A. Herrmann, and G. van Meer Tracking down lipid flippases and their biological functions J. Cell Sci., February 22, 2004; 117(6): 805 - 813. [Abstract] [Full Text] [PDF] |
||||
![]() |
S. Chantalat, S.-K. Park, Z. Hua, K. Liu, R. Gobin, A. Peyroche, A. Rambourg, T. R. Graham, and C. L. Jackson The Arf activator Gea2p and the P-type ATPase Drs2p interact at the Golgi in Saccharomyces cerevisiae J. Cell Sci., February 15, 2004; 117(5): 711 - 722. [Abstract] [Full Text] [PDF] |
||||
![]() |
F. J. Perez-Victoria, F. Gamarro, M. Ouellette, and S. Castanys Functional Cloning of the Miltefosine Transporter: A NOVEL P-TYPE PHOSPHOLIPID TRANSLOCASE FROM LEISHMANIA INVOLVED IN DRUG RESISTANCE J. Biol. Chem., December 12, 2003; 278(50): 49965 - 49971. [Abstract] [Full Text] [PDF] |
||||
![]() |
Z. Hua and T. R. Graham Requirement for Neo1p in Retrograde Transport from the Golgi Complex to the Endoplasmic Reticulum Mol. Biol. Cell, December 1, 2003; 14(12): 4971 - 4983. [Abstract] [Full Text] [PDF] |
||||
![]() |
P. K. Hanson, L. Malone, J. L. Birchmore, and J. W. Nichols Lem3p Is Essential for the Uptake and Potency of Alkylphosphocholine Drugs, Edelfosine and Miltefosine J. Biol. Chem., September 19, 2003; 278(38): 36041 - 36050. [Abstract] [Full Text] [PDF] |
||||
![]() |
T. Pomorski, R. Lombardi, H. Riezman, P. F. Devaux, G. van Meer, and J. C. M. Holthuis Drs2p-related P-type ATPases Dnf1p and Dnf2p Are Required for Phospholipid Translocation across the Yeast Plasma Membrane and Serve a Role in Endocytosis Mol. Biol. Cell, March 1, 2003; 14(3): 1240 - 1254. [Abstract] [Full Text] [PDF] |
||||