Sec14p-like proteins regulate phosphoinositide homoeostasis and intracellular protein and lipid trafficking in yeast.
The major PI (phosphatidylinositol)/PC (phosphatidylcholine)-transfer protein in yeast, Sec14p, co-ordinates lipid metabolism with protein transport from the Golgi complex. Yeast also express five additional gene products that share 24-65% primary sequence identity with Sec14p. These Sec14p-like proteins are termed SFH (Sec Fourteen Homologue) proteins, and overexpression of certain individual SFH gene products rescues sec14-1(ts)-associated growth and secretory defects. SFH proteins are atypical in that these stimulate the transfer of PI, but not PC, between distinct membrane bilayer systems in vitro. Further analysis reveals that SFH proteins functionally interact with the Stt4p phosphoinositide 4-kinase to stimulate PtdIns(4,5)P(2) synthesis which in turn activates phospholipase D. Finally, genetic analyses indicate that Sfh5p interfaces with the function of specific subunits of the exocyst complex as well as the yeast SNAP-25 (25 kDa synaptosome-associated protein) homologue, Sec9p. Our current view is that Sfh5p regulates PtdIns(4,5)P(2) homoeostasis at the plasma membrane, and that Sec9p responds to that regulation. Thus SFH proteins individually regulate specific aspects of lipid metabolism that couple, with exquisite specificity, with key cellular functions.
Mousley
C J
CJ
Department of Cell and Developmental Biology, Lineberger Comprehensive Cancer Center, School of Medicine, University of North Carolina at Chapel Hill, 27599-7090, U.S.A.
Tyeryar
K R
KR
Ryan
M M
MM
Bankaitis
V A
VA
D001693:Biological Transport, Active; D006706:Homeostasis / Q000502:physiology*; D007424:Intracellular Fluid / Q000737:chemistry / Q000378:metabolism*; D005810:Multigene Family; D010716:Phosphatidylinositols / Q000737:chemistry / Q000378:metabolism*; D049294:Phospholipid Transfer Proteins / Q000737:chemistry / Q000502:physiology*; D021381:Protein Transport / Q000502:physiology; D012441:Saccharomyces cerevisiae / Q000737:chemistry / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000737:chemistry / Q000502:physiology*
C483430:CSR1 protein, S cerevisiae; D010716:Phosphatidylinositols; D049294:Phospholipid Transfer Proteins; C483438:SEC14 protein, S cerevisiae; C483439:SFH5 protein, S cerevisiae; D029701:Saccharomyces cerevisiae Proteins