QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

Vol. 17, Issue 6, 2498-2512, June 2006

This Article Full Text Full Text (PDF) Supplemental Material All Versions of this Article: E06-01-0089v1 17/6/2498    most recent Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Phillips, S. E. Articles by Bankaitis, V. A. Search for Related Content PubMed PubMed Citation Articles by Phillips, S. E. Articles by Bankaitis, V. A.

Specific and Nonspecific Membrane-binding Determinants Cooperate in Targeting Phosphatidylinositol Transfer Protein -Isoform to the Mammalian Trans-Golgi Network

Scott E. Phillips^*,, Kristina E. Ile^*,, Malika Boukhelifa^*, Richard P.H. Huijbregts, and Vytas A. Bankaitis^*

*Department of Cell and Developmental Biology, Lineberger Comprehensive Cancer Center, University of North Carolina School of Medicine, Chapel Hill, NC 27599-7090; and Department of Biochemistry and Molecular Genetics, University of Alabama at Birmingham, Birmingham, AL 35294-0021

Submitted January 30, 2006; Revised February 13, 2006; Accepted March 6, 2006
Monitoring Editor: Reid Gilmore

Phosphatidylinositol transfer proteins (PITPs) regulate the interface between lipid metabolism and specific steps in membrane trafficking through the secretory pathway in eukaryotes. Herein, we describe the cis-acting information that controls PITP localization in mammalian cells. We demonstrate PITP localizes predominantly to the trans-Golgi network (TGN) and that this localization is independent of the phospholipid-bound state of PITP. Domain mapping analyses show the targeting information within PITP consists of three short C-terminal specificity elements and a nonspecific membrane-binding element defined by a small motif consisting of adjacent tryptophan residues (the W₂₀₂W₂₀₃ motif). Combination of the specificity elements with the W₂₀₂W₂₀₃ motif is necessary and sufficient to generate an efficient TGN-targeting module. Finally, we demonstrate that PITP association with the TGN is tolerant to a range of missense mutations at residue serine 262, we describe the TGN localization of a novel PITP isoform with a naturally occurring S₂₆₂Q polymorphism, and we find no other genetic or pharmacological evidence to support the concept that PITP localization to the TGN is obligately regulated by conventional protein kinase C (PKC) or the Golgi-localized PKC isoforms or . These latter findings are at odds with a previous report that conventional PKC-mediated phosphorylation of residue Ser₂₆₂ is required for PITP targeting to Golgi membranes.

The online version of this article contains supplemental material at MBC Online (http://www.molbiolcell.org).

These authors contributed equally to this work.

Address correspondence to: Vytas A. Bankaitis ( vytas{at}med.unc.edu)

Abbreviations used: GFP, green fluorescent protein; MEF, murine embryonic fibroblast; PITP, phosphatidylinositol transfer protein; PtdCho, phosphatidylcholine; PtdIns, phosphatidylinositol; SM, sphingomyelin; TGN, trans-Golgi network

This article has been cited by other articles:

				Y. Liu, M. Boukhelifa, E. Tribble, E. Morin-Kensicki, A. Uetrecht, J. E. Bear, and V. A. Bankaitis The Sac1 Phosphoinositide Phosphatase Regulates Golgi Membrane Morphology and Mitotic Spindle Organization in Mammals Mol. Biol. Cell, July 1, 2008; 19(7): 3080 - 3096. [Abstract] [Full Text] [PDF]

				N. Kudo, K. Kumagai, N. Tomishige, T. Yamaji, S. Wakatsuki, M. Nishijima, K. Hanada, and R. Kato Structural basis for specific lipid recognition by CERT responsible for nonvesicular trafficking of ceramide PNAS, January 15, 2008; 105(2): 488 - 493. [Abstract] [Full Text] [PDF]

				J. G. Alb Jr., S. E. Phillips, L. R. Wilfley, B. D. Philpot, and V. A. Bankaitis The pathologies associated with functional titration of phosphatidylinositol transfer protein {alpha} activity in mice J. Lipid Res., August 1, 2007; 48(8): 1857 - 1872. [Abstract] [Full Text] [PDF]