Specific and nonspecific membrane-binding determinants cooperate in targeting phosphatidylinositol transfer protein beta-isoform to the mammalian trans-Golgi network. Academic Article uri icon


  • 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 PITPbeta localization in mammalian cells. We demonstrate PITPbeta localizes predominantly to the trans-Golgi network (TGN) and that this localization is independent of the phospholipid-bound state of PITPbeta. Domain mapping analyses show the targeting information within PITPbeta 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 W(202)W(203) motif). Combination of the specificity elements with the W(202)W(203) motif is necessary and sufficient to generate an efficient TGN-targeting module. Finally, we demonstrate that PITPbeta association with the TGN is tolerant to a range of missense mutations at residue serine 262, we describe the TGN localization of a novel PITPbeta isoform with a naturally occurring S262Q polymorphism, and we find no other genetic or pharmacological evidence to support the concept that PITPbeta localization to the TGN is obligately regulated by conventional protein kinase C (PKC) or the Golgi-localized PKC isoforms delta or epsilon. These latter findings are at odds with a previous report that conventional PKC-mediated phosphorylation of residue Ser262 is required for PITPbeta targeting to Golgi membranes.

published proceedings

  • Mol Biol Cell

author list (cited authors)

  • Phillips, S. E., Ile, K. E., Boukhelifa, M., Huijbregts, R., & Bankaitis, V. A.

citation count

  • 35

complete list of authors

  • Phillips, Scott E||Ile, Kristina E||Boukhelifa, Malika||Huijbregts, Richard PH||Bankaitis, Vytas A

editor list (cited editors)

  • Gilmore, R.

publication date

  • June 2006