Platelets are necessary for normal hemostasis. The abnormal aggregation of platelets is associated with myocardial infarction and stroke in humans. It is therefore very important to understand the mechanisms leading to platelet aggregation via platelet integrin alphaIIbbeta3 signaling. Previously, our lab identified a novel alphaIIb cytoplasmic tail binding protein CIB (calcium and integrin binding protein) from a human fetal liver cDNA library in the yeast two-hybrid system. The protein has high sequence homology to calcineurin B (58%) and calmodulin (56%) and thus may play an important role in integrin signaling. Although alphaIIbbeta3 is found only in platelets and their precusor megakaryocytes, our lab found that CIB is expressed in a wide variety of tissues and cell types, suggesting that CIB may also have important functions independent of platelets. To determine if CIB plays a role in development, I will determine its tissue expression pattern during murine development in order to predict which organs might be most affected by its absence. I will also generate a CIB knockout mouse and compare the development of the knockout mouse to the normal mouse. If live -/- mice are obtained, I will analyze the function of platelets from these mice compared to wild type littermates, with a specific focus on alphaIIbbeta3 integrin function. Finally, I will produce a transgenic mouse model that overexpresses CIB specifically in the megakaryocytic lineage. This model will be used to further examine the effects of CIB on alphaIIbbeta3 integrin function and to address the possibility that CIB plays a role in platelet microparticle formation. Overall, these studies will provide experimental models to probe the function of CIB in integrin dependent and independent functions.
| Yuan, Weiping; Leisner, Tina M; McFadden, Andrew W et al. (2006) CIB1 is essential for mouse spermatogenesis. Mol Cell Biol 26:8507-14 |
| Yuan, Weiping; Leisner, Tina M; McFadden, Andrew W et al. (2006) CIB1 is an endogenous inhibitor of agonist-induced integrin alphaIIbbeta3 activation. J Cell Biol 172:169-75 |
