Renhao Li Lab:Research
Regulation of Ectodomain Shedding
Ectodomain shedding is a process in which an integral membrane protein is proteolytically cleaved and its extracellular domain released from the cell. It affects many membrane proteins including growth factor precursors, amyloid precursor proteins, cytokines, cell adhesion receptors, and proteoglycans. Excessive shedding activity often leads to diseases such as cancer, arthritis and neurodegenerative diseases. We are interested in elucidating the molecular mechanisms underlying regulation of ectodomain shedding by intracellular events including protein interactions with the cytoplasmic domain of shedding substrates. The following questions drive our current studies in the lab:
- test
- test again
In parallel, we aim to, based on what we have learned of the regulation mechanisms, devise ways to inhibit and modulate shedding of membrane protein substrates, particularly those with significant implications in human diseases.
Structure and Regulation of Platelet GPIb-IX-V Complex
The glycoprotein (GP)Ib-IX-V complex (a.k.a. CD42) is one of the major hubs on the platelet surface for its aggregation and activation. Malfunction or lack of the GPIb-IX-V complex in platelets results in severe bleeding disorders, and it plays a critical role in a number of cardiovascular diseases including myocardial infarction and stroke. The interaction between the glycoprotein (GP)Ib-IX-V complex on the platelet surface and von Willebrand factor (VWF) that marks the injury site in the artery is widely considered as the first step for hemostasis. Upon binding to VWF, the GPIb-IX-V complex transduces into the platelet an activating signal, leading eventually to platelet aggregation and thrombus formation. The GPIb-IX-V complex consists of nine subunits of four kinds: GPIbα, GPIbβ, GPIX and GPV. Our current focus is to delineate the 3-dimensional organization of the complex, that is, how these subunits evolve, interact with one another and assemble into the functional receptor complex. The insights on the overall organization of the GPIb-IX-V complex will help us understand how it mediates signals of VWF-binding across the plasma membrane to activate the platelet, and how the binding activity of this complex is regulated by intracellular signals.
Mechanisms of ITP
to be updated
