PV-1 labels trans-cellular openings in mouse endothelial cells and is negatively regulated by VEGF.
The PV-1 protein is endogenously expressed from a single mRNA in the mouse pancreatic MS-1 endothelial cell line as a 60-kDa N-glycosylated and 50-kDa non-glycosylated protein that form DTT sensitive oligomers. In the absence of cell permeabilization, PV-1 antibodies label transcellular openings of variable size, many that penetrate through the cytosol with circular openings on the free and attached surface of the plasma membrane. Intracellular PV-1 is localized in perinuclear aggregates that can extend as a fibrous network through the cytosol and often surround the nuclear compartment. In some cells, PV-1 is organized as a large unipolar spindle-like structure that is often associated with severe deformation of the nucleus. The VEGF-R2 inhibitor SU5614 increased the PV-1 protein levels in a dose-dependent manner and inhibited MS-1 cell growth, without inducing apoptosis. This report provides compelling evidence for a functional role of PV-1 in the formation of large transendothelial channels and modulation of nuclear shape. Moreover, these data suggest the PV-1 protein is negatively regulated by VEGF.
Hnasko
Robert
R
United States Department of Agriculture, Agricultural Research Service-Pacific West Area, Western Region Research Center, Foodborne Contaminants Research Unit, Albany, California, USA.
Carter
John Mark
JM
Medina
Freddy
F
Frank
Philippe G
PG
Lisanti
Michael P
MP
D000818:Animals; D002352:Carrier Proteins / Q000032:analysis* / Q000378:metabolism*; D002460:Cell Line; D021961:Cell Membrane Structures / Q000737:chemistry* / Q000648:ultrastructure; D002467:Cell Nucleus / Q000737:chemistry / Q000648:ultrastructure; D049109:Cell Proliferation / Q000187:drug effects; D003593:Cytoplasm / Q000737:chemistry; D015536:Down-Regulation; D042783:Endothelial Cells / Q000737:chemistry* / Q000378:metabolism* / Q000648:ultrastructure; D007211:Indoles / Q000494:pharmacology; D008565:Membrane Proteins / Q000032:analysis* / Q000378:metabolism*; D051379:Mice; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000037:antagonists & inhibitors / Q000378:metabolism*
D002352:Carrier Proteins; D007211:Indoles; D008565:Membrane Proteins; C486772:Plvap protein, mouse; C416849:SU 5614; D040301:Vascular Endothelial Growth Factor Receptor-2