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How cells accurately duplicate and segregate their genetic information remains a topic of intense research. A series of specially commissioned articles in this issue presents recent insights into different aspects of the cell division cycle and genomic surveillance.
Successful completion of meiosis in vertebrate oocytes requires the localization and maintenance of the meiotic spindle at the cell cortex. Arp2/3-nucleated actin filaments are now shown to flow away from the cortex overlying the spindle, resulting in cytoplasmic streaming, which maintains the spindle in its asymmetric position.
In yeast, polarized localization of Cdc42 is essential for budding and mating, but how polarity is attained has been elusive. Grinstein and colleagues show that phosphatidylserine accumulates in a polar fashion in yeast, and is required for the proper localization of Cdc42.
In humans, mutations in the DNA-damage-response modulator MCPH1 are associated with defective neural development. Wang and colleagues show that mutations in mouse MCPH1 result in microcephaly through the delocalization of Chk1 from centrosomes, causing the uncoupling of mitosis and centrosome duplication, and resulting in spindle misorientation and a switch in the fate of neural stem cell daughters.
In the TGFβ pathway, receptor-activated SMADs (R-SMADs) associate with SMAD4 to regulate transcription. Piccolo and colleagues reveal that the deubiquitylase USP15 is required for TGFβ responses by reversing R-SMAD ubiquitylation and thereby promoting the retention of the SMAD complex at promoters.
Non-enveloped viruses such as SV40 are transported from the extracellular space into the host cell nucleus through a pathway involving endocytosis, trafficking to the endoplasmic reticulum (ER) lumen, transport across the ER membrane to the cytoplasm, and subsequent nuclear import. Helenius and colleagues provide insight into how SV40 escapes from the ER by showing that viral proteins interact with components of the host ER-associated degradation machinery (ERAD). These interactions are crucial for translocation of SV40 into the cytoplasm and infectivity.
Ivaska and colleagues identify SHARPIN as an inhibitor of integrin activity in an RNAi screen for integrin regulators. They show that SHARPIN acts by binding to the cytoplasmic domain of integrin α-subunits and reduces the recruitment of talin and kindlin to the β-subunits.
A potential role for glycosphingolipids and lipid rafts in apical sorting was initially met with enthusiasm, but genetic analysis has since provided little support for it. A report now establishes that glycosphingolipids mediate apical sorting, and specifically help maintain apicobasal polarity in Caenorhabditis elegans.
The spindle assembly checkpoint halts cell-cycle progression in the presence of unattached kinetochores by preventing activation of APC/C. Pines and colleagues find that APC15 has a critical role in regulating APC/C activation by promoting release of the inhibitory MCC complex from APC/C once the spindle assembly checkpoint is satisfied.
ATP production by mitochondria requires the efficient flow of protons through the F1FO ATP-synthase complex. Jonas and colleagues show that Bcl-xL interacts with the F1FO complex in the mitochondrial matrix and increases the efficiency of this enzyme by decreasing proton leak.
Cell polarity is critically important for organogenesis. Using a series of RNA-interference-based screens, Göbel and colleagues reveal the role of the glycosphingolipid glucosylceramide (GlcCer) in determining apicobasal polarity and maintaining the organization of the intestinal lumen in the developing worm.