WD repeat-containing protein 5 (WDR5) localizes to the midbody and regulates abscission.

Cytokinesis partitions the cytoplasm of a parent cell into two daughter cells and is essential for the completion of cell division. The final step of cytokinesis in animal cells is abscission, which is a process leading to the physical separation of two daughter cells. Abscission requires membrane traffic and microtubule disassembly at a specific midbody region called the secondary ingression. Here, we report that WD repeat-containing protein 5 (WDR5), a core subunit of COMPASS/MLL family histone H3 lysine 4 methyltransferase (H3K4MT) complexes, resides at the midbody and associates with a subset of midbody regulatory proteins, including PRC1 and CYK4/MKLP1. Knockdown of WDR5 impairs abscission and increases the incidence of multinucleated cells. Further investigation revealed that the abscission delay is primarily due to slower formation of secondary ingressions in WDR5 knockdown cells. Consistent with these defects, midbody microtubules in WDR5 knockdown cells also display enhanced resistance to depolymerization by nocodazole. Recruitment of WDR5 to the midbody dark zone appears to require integrity of the WDR5 central arginine-binding cavity, as mutations that disrupt histone H3 and MLL1 binding to this pocket also abolish the midbody localization of WDR5. Taken together, these data suggest that WDR5 is specifically targeted to the midbody in the absence of chromatin and that it promotes abscission, perhaps by facilitating midbody microtubule disassembly.

[ER-alpha, IGF-1R expressions and co-expressions in newborn rats with experimental hypoxic-ischemic brain damage].

OBJECTIVE: To observe the distribution and change of insulin-like growth factor-1 receptor (IGF-1R), estrogen receptor-alpha (ER-alpha) and their co-expression in the brains of normal newborn female rats and in the brains of those with hypoxic-ischemic brain damage (HIBD). METHODS: The 7 day-old female SD rats were subjected to the ligation of right carotid artery (ischemia), then they were put into a box full with 8% oxygen and 92% nitrogen for an hour (hypoxia). The methods of immunohistochemistry and double-immunohistochemistry were used to detect the expression of IGF-1R, ER-alpha and their co-expression in the brain. RESULTS: (1) There were extensive immunoreactions of IGF-IR, ER-alpha in newborn rat's brain, and there were extensive co-localization of IGF-1R and ER-alpha in the same cells of cerebral cortex. (2) There were no changes in the expressions of IGF-1R and ER-alpha, no changes in the co-expression of IGF-1R and ER-alpha at 24 hours of HIBD; whereas there were increasing expressions of IGF-1R, ER-alpha and increasing co-expression of IGF-1R, ER-alpha in the cerebral cortex on the 7th day of HIBD. CONCLUSION: The above results suggest that there are co-action of IGF-1R and ER-alpha in the repair of hypoxic-ischemic brain damage.