Identification of abscission checkpoint bodies as structures that regulate ESCRT factors to control abscission timing.

The abscission checkpoint regulates the ESCRT membrane fission machinery and thereby delays cytokinetic abscission to protect genomic integrity in response to residual mitotic errors. The checkpoint is maintained by Aurora B kinase, which phosphorylates multiple targets, including CHMP4C, a regulatory ESCRT-III subunit necessary for this checkpoint. We now report the discovery that cytoplasmic abscission checkpoint bodies (ACBs) containing phospho-Aurora B and tri-phospho-CHMP4C develop during an active checkpoint. ACBs are derived from mitotic interchromatin granules, transient mitotic structures whose components are housed in splicing-related nuclear speckles during interphase. ACB formation requires CHMP4C, and the ESCRT factor ALIX also contributes. ACB formation is conserved across cell types and under multiple circumstances that activate the checkpoint. Finally, ACBs retain a population of ALIX, and their presence correlates with delayed abscission and delayed recruitment of ALIX to the midbody where it would normally promote abscission. Thus, a cytoplasmic mechanism helps regulate midbody machinery to delay abscission.

When a cell divides, it must first carefully duplicate its genetic information and package these copies into compartments housed in the two new cells. Errors in this process lead to genetic mistakes that trigger cancer or other harmful biological events. Quality control checks exist to catch errors before it is too late. This includes a final 'abscission' checkpoint right before the end of division, when the two new cells are still connected by a thin membrane bridge. If cells fail to pass this 'no cut' checkpoint, they delay severing their connection until the mistake is fixed. A group of proteins called ESCRTs is responsible for splitting the two cells apart if nothing is amiss. The abscission checkpoint blocks this process by altering certain proteins in the ESCRT complex, but exactly how this works is not yet clear. To find out more, Williams et al. imaged ESCRT factors in a new experimental system in which the abscission checkpoint is active in many cells. This showed that, in this context, certain ESCRT components were rerouted from the thread of membrane between the daughter cells to previously unknown structures, which Williams et al. named abscission checkpoint bodies. These entities also sequestered other factors that participate in the abscission checkpoint and factors that contribute to gene expression. These results are key to better understand how cells regulate their division; in particular, they provide a new framework to explore when this process goes wrong and contributes to cancer.

Pituitary macroadenomas with oculomotor cistern extension and tracking: implications for surgical management.

OBJECT Oculomotor cistern extension of pituitary adenomas is an overlooked feature within the literature. In this study, 7 cases of pituitary macroadenoma with oculomotor cistern extension and tracking are highlighted, and the implications of surgical and medical management are discussed. METHODS The records of patients diagnosed with pituitary macroadenomas who underwent resection and in whom preoperative pituitary protocol MRI scans were available for review were retrospectively reviewed. The patient and tumor characteristics were reviewed along with the operative outcomes and complications. RESULTS Seven patients (4.1%) with oculomotor cistern extension and tracking were identified in a cohort of 170 patients with pituitary macroadenoma. The most common presenting symptoms were visual deficit (6 patients; 86%), apoplexy (3 patients; 43%), and oculomotor nerve palsy (3 patients; 43%). Lone oculomotor nerve palsy was seen in 2 patients without apoplexy and 1 patient with an apoplectic event. Gross-total resection was achieved via a microscopic endonasal transsphenoidal approach with or without endoscopic aid to the sella in 14%, near-total resection in 29%, and subtotal resection in 57% of patients in the data set. CONCLUSIONS Pituitary adenoma extension along the oculomotor cistern is uncommon; however, preoperatively recognizing such extension should play an important role in the surgeon's operative considerations and postoperative clinical management because this extension can limit gross-total resection using the transsphenoidal approach alone.