KRIT1/cerebral cavernous malformation 1 protein localizes to vascular endothelium, astrocytes and pyramidal cells of the adult human cerebral cortex

OBJECTIVE:, Mutations in KRIT1 cause familial cerebral cavernous malformation, an autosomal dominant disorder affecting primarily the central nervous system vasculature. . Although recent studies have suggested that Krev-1 interaction trapped 1(KRIT1) is a microtubule-associated protein that interacts with integrin cytoplasmic domain- associated protein-1alpha, the function of KRIT1 remains elusive. METHODS: We used Western blotting and immunohistochemistry with specific KRIT1 polyclonal antibodies to investigate KRIT1 protein expression, in diverse cerebral and, extracerebral tissues. RESULTS: Immunostaining demonstrates that although KRIT1 is expressed in a broad variety of human organs, it localizes,to the vascular endothelium of each, specifically to capillaries and arterioles. KRIT1 antibody fails to stain fenestrated caoillaribs in the kidney, the liver, or the red pulp of the spleen,,where,endothelial cells do not to adhere to one, another. In contrast, intense staining is observed in, the I thymus and the,white pulp of the spleen, where specialized blood-organ barriers bare formed. Other cell types, including various epithelia, cardiac hepatocytes, and hepatocytes, also stain with KRIT1 CONCLUSION: Although KRIT1 expression is seen in every endothlelium studied, cerebral cavernous malformation lesions are seen almost exclusively in the central nervous system, suggesting that additional cell -type('s) contribute to- th I e pathophysiology of cerebral cavernous malformations. Here, we demonstrate that KRIT1 is also present in cells and structures integral to the cerebral angiogenesis and,formation of the blood-brain barrier, namely, endothelial cells and astrocytic foot, processes, as well as pyramidal neurons in the cerebral cortex.