Mutations in Krev1 interaction trapped gene 1 (KRIT1) cause cerebral cavernous 
malformation, an autosomal dominant disease featuring malformation of cerebral 
capillaries resulting in cerebral hemorrhage, strokes, and seizures. The 
biological functions of KRIT1 are unknown. We have investigated KRIT1 expression 
in endothelial cells by using specific anti-KRIT1 antibodies. By both microscopy 
and coimmunoprecipitation, we show that KRIT1 colocalizes with microtubules. In 
interphase cells, KRIT1 is found along the length of microtubules. During 
metaphase, KRIT1 is located on spindle pole bodies and the mitotic spindle. 
During late phases of mitosis, KRIT1 localizes in a pattern indicative of 
association with microtubule plus ends. In anaphase, the plus ends of the 
interpolar microtubules show strong KRIT1 staining and, in late telophase, KRIT1 
stains the midbody remnant most strongly; this is the site of cytokinesis where 
plus ends of microtubules from dividing cells overlap. These results establish 
that KRIT1 is a microtubule-associated protein; its location at plus ends in 
mitosis suggests a possible role in microtubule targeting. These findings, 
coupled with evidence of interaction of KRIT1 with Krev1 and integrin 
cytoplasmic domain-associated protein-1 alpha (ICAP1 alpha), suggest that KRIT1 
may help determine endothelial cell shape and function in response to cell-cell 
and cell-matrix interactions by guiding cytoskeletal structure. We propose that 
the loss of this targeting function leads to abnormal endothelial tube 
formation, thereby explaining the mechanism of formation of cerebral cavernous 
malformation (CCM) lesions.