This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Integrins are cell surface receptors that serve a number of basic cellular functions. One of these functions, which is relevant to the organ edema that occurs in inflammatory diseases like acute lung injury, is the regulation of passage of fluid and solute across the endothelium, the layer of cells lining blood vessels throughout the circulatory system. The Sheppard lab has recently demonstrated that alpha-v integrins modulate endothelial permeability by organizing the actin cytoskeleton. Specifically, alpha-v beta-3 integrin is necessary for rearrangement of actin into cortical distribution that increases vascular barrier strength in response to sphingosine 1-phosphate, a plasma borne barrier-enhancing molecule;on the other hand, alpha-v beta-5 is required for organization of the cytoskeleton into stress fibers that decrease barrier strength in response to thrombin, a blood borne mediator of increased blood vessel leakiness. Our objective is to identify the constituents of the protein complexes associated with these integrins. An ideal approach in this regard is to employ mass spectrometry, where biochemically isolated integrin complexes can be submitted to mass spectrometric sequencing for protein discovery. With this unbiased approach, the distinct actin binding and/or modulatory proteins associated with these two integrins may be identified and studied further to understand how they modulate actin organization. Armed with this powerful information, we may further dissect pathways mediating the opposing biological response of these two integrins and target specific points along their respective pathways as potential treatments for organ edema in the setting of sepsis and other acute inflammatory diseases.

Agency
National Institute of Health (NIH)
Institute
National Center for Research Resources (NCRR)
Type
Biotechnology Resource Grants (P41)
Project #
2P41RR001614-28
Application #
8169819
Study Section
Special Emphasis Panel (ZRG1-BCMB-M (40))
Project Start
2010-09-12
Project End
2011-05-31
Budget Start
2010-09-12
Budget End
2011-05-31
Support Year
28
Fiscal Year
2010
Total Cost
$1,766
Indirect Cost
Name
University of California San Francisco
Department
Pharmacology
Type
Schools of Pharmacy
DUNS #
094878337
City
San Francisco
State
CA
Country
United States
Zip Code
94143
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