StarD10, a START domain protein overexpressed in breast cancer, functions as a phospholipid transfer protein.
We originally identified StarD10 as a protein overexpressed in breast cancer that cooperates with the ErbB family of receptor tyrosine kinases in cellular transformation. StarD10 contains a steroidogenic acute regulatory protein (StAR/StarD1)-related lipid transfer (START) domain that is thought to mediate binding of lipids. We now provide evidence that StarD10 interacts with phosphatidylcholine (PC) and phosphatidylethanolamine (PE) by electron spin resonance measurement. Interaction with these phospholipids was verified in a fluorescence resonance energy transfer-based assay with 7-nitro-2,1,3-benzoxadiazol-4-yl-labeled lipids. Binding was not restricted to lipid analogs since StarD10 selectively extracted PC and PE from small unilamellar vesicles prepared with endogenous radiolabeled lipids from Vero monkey kidney cells. Mass spectrometry revealed that StarD10 preferentially selects lipid species containing a palmitoyl or stearoyl chain on the sn-1 and an unsaturated fatty acyl chain (18:1 or 18:2) on the sn-2 position. StarD10 was further shown to bind lipids in vivo by cross-linking of protein expressed in transfected HEK-293T cells with photoactivable phosphatidylcholine. In addition to a lipid binding function, StarD10 transferred PC and PE between membranes. Interestingly, these lipid binding and transfer specificities distinguish StarD10 from the related START domain proteins Pctp and CERT, suggesting a distinct biological function.
Olayioye
Monilola A
MA
The Walter and Eliza Hall Institute of Medical Research, 1G Royal Parade, Victoria 3050, Australia.
Vehring
Stefanie
S
Müller
Peter
P
Herrmann
Andreas
A
Schiller
Jürgen
J
Thiele
Christoph
C
Lindeman
Geoffrey J
GJ
Visvader
Jane E
JE
Pomorski
Thomas
T
D000818:Animals; D001943:Breast Neoplasms / Q000737:chemistry*; D045744:Cell Line, Tumor; D005227:Fatty Acids / Q000032:analysis; D006801:Humans; D008051:Lipid Bilayers / Q000378:metabolism; D008055:Lipids / Q000032:analysis / Q000737:chemistry; D008565:Membrane Proteins / Q000378:metabolism* / Q000502:physiology; D010713:Phosphatidylcholines / Q000378:metabolism; D010714:Phosphatidylethanolamines / Q000378:metabolism; D049294:Phospholipid Transfer Proteins / Q000378:metabolism* / Q000502:physiology; D010750:Phosphoproteins / Q000378:metabolism / Q000502:physiology*; D011485:Protein Binding; D013379:Substrate Specificity
D005227:Fatty Acids; D008051:Lipid Bilayers; D008055:Lipids; D008565:Membrane Proteins; D010713:Phosphatidylcholines; D010714:Phosphatidylethanolamines; D049294:Phospholipid Transfer Proteins; D010750:Phosphoproteins; C488090:STARD10 protein, human