Plvap/PV1 critical to formation of the diaphragms in endothelial cells

Dartmouth scientists have demonstrated the importance of the gene Plvap and the structures it forms in mammalian physiology in a study published in December by the journal Developmental Cell.

"The knowledge generated and the animal models created will allow a better understanding of the role of the gene in diseases and will help validate its usefulness as a therapeutic or diagnostic ," said lead author Radu V. Stan, MD, associate professor, Geisel School of Medicine at Dartmouth, and member of the Dartmouth-Hitchcock Norris Cotton Cancer Center (NCCC).

The study demonstrates that plasmalemma vesicle associated protein (PV1), a vertebrate gene specifically expressed in the vascular endothelial cells, is critical for the formation of the diaphragms of endothelial caveolae, fenestrae and transendothelial channels. Although discovered in the 1960s by , the function of the diaphragms was previously unknown. Using mice with loss and gain of PV1 function Dartmouth scientists demonstrated that the diaphragms of fenestrae are critical for maintenance of basal permeability, the homeostasis of in terms of protein and lipid blood composition, and ultimately survival.

PV1 has newly discovered roles in cancer and in various infectious and . "The knowledge generated and the animal models created will allow a better understanding of the role of the gene in these diseases and to validate its usefulness as a therapeutic or diagnostic target," said Stan.

In the absence of such diaphragms, extravasation produces a noninflammatory protein-losing enteropathy resulting in protein calorie malnutrition and ultimately death.

"Our results and the mouse models we have created provide the foundations for evaluating numerous aspects of basal permeability in fenestrated vascular beds," said Stan.

Related Stories

Unique role for blood formation gene identified

date Sep 12, 2007

All blood cell production in adults depends on the steady work of a vital gene that if lost results in early bone marrow failure, Dartmouth Medical School cancer geneticists have found. Their research reveals an unexpected ...

Feedback loop maintains basal cell population

date Nov 01, 2012

Notch – the protein that can help determine cell fate – maintains a stable population of basal cells in the prostate through a positive feedback loop system with another key protein – TGF beta (transforming growth factor ...

Enzyme offers new therapeutic target for cancer drugs

date Jun 21, 2012

Researchers at the University of California, San Diego School of Medicine have uncovered a new signal transduction pathway specifically devoted to the regulation of alternative RNA splicing, a process that allows a single ...

Recommended for you

DNA blood test detects lung cancer mutations

date 11 hours ago

Cancer DNA circulating in the bloodstream of lung cancer patients can provide doctors with vital mutation information that can help optimise treatment when tumour tissue is not available, an international group of researchers ...

Tumors prefer the easy way out

date 13 hours ago

Tumor cells become lethal when they spread. Blocking this process can be a powerful way to stop cancer. Historically, scientists thought that tumor cells migrated by brute force, actively pushing through whatever ...

Brain tumors may be new targets of Ebola-like virus

date 13 hours ago

Brain tumors are notoriously difficult for most drugs to reach, but Yale researchers have found a promising but unlikely new ally against brain cancers—portions of a deadly virus similar to Ebola.

User comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.