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The human genome encodes at least 70 Rab GTPases and more than 50 putative Rab GTPase-activating proteins (GAPs). An elegant scheme to rapidly identify the Rab target for each of these GAPs has led to the identification of a potent Rab GAP for Rab5.
Asymmetric cell division is a fundamental process by which cells give rise to progenies with different fates. Although this mechanism is well studied in the worm and fly, mammalian asymmetric cell division is poorly understood. The finding that Gβγ and AGS3 can control mitotic spindle orientation and progenitor cell fates during mouse cortical development suggests evolutionarily conserved roles in asymmetric cell division.
Phosphoinositide 3-kinases (PI(3)Ks) are mainly known for their lipid kinase activity in various cellular functions; however, PI(3)Ks also have protein kinase activity. Non-muscle tropomyosin has been identified as a novel protein target for PI(3)Kγ. Phosphorylation of tropomyosin is required for β-adrenergic receptor internalization, providing new insight into PI(3)K function during clathrin-mediated endocytosis.
It has long been thought that gathering chromosomes during spindle assembly is exclusively the responsibility of microtubules. However, a recent study by Lénárt et al. shows that, in larger cells, a collapsing network of actin filaments ensnares and transports the chromosomes, bringing them in range for microtubule capture.
Cell migration requires that Rac GTPases promote formation of actin polymers at the cell's leading edge. An activator of Rac, DOCK180, accomplishes this localization by using its DHR-1 domain to bind phosphatidylinositol-3,4,5-trisphosphate at the membrane.
Cdk2 is thought to regulate entry into S phase, whereas Cdk1 controls the initiation of mitosis. New evidence shows that Cdk1 is equally capable of promoting the G1/S transition in Cdk2−/− cells, raising the question as to whether Cdk1 constitutes the predominant cyclin-dependent kinase in mammalian cells, or only compensates for Cdk2 function when it is compromised.
The Nbs1 protein participates in the cell-cycle checkpoint response to DNA double-strand breaks (DSBs), but its precise mode of action — especially in relation to the checkpoint kinase Atm — has been debated. New mouse models suggest that Nbs1 is required for activation of Atm in response to DNA DSBs and that it also functions in an amplification loop with Atm that allows even a small number of DNA DSBs to mount a potent checkpoint response.
Many viruses and toxins enter the cytoplasm of cells by crossing endosomal membranes. New evidence now suggests that if entry occurs through multivesicular bodies, then they are first delivered into intraluminal vesicles before their final transfer into the cytoplasm via the 'back-fusion' of these vesicles.
Cytoplasmic processing bodies, also known as P-bodies, concentrate enzymes that are involved in mRNA turnover and sequester mRNAs away from the translational machinery. Strong evidence now connects the RNA interference machinery with P-body formation.
New work reveals a key signal transduction pathway through which nitric oxide (NO) regulates apoptosis induced by disparate cellular stresses. Glyceraldehyde-3-phosphate dehydrogenase (GAPDH) is S-nitrosylated by NO, which initiates an interaction with the E3 ligase Siah1, leading to nuclear translocation and ubiquitin-mediated degradation of nuclear target proteins.
The small GTPase Ran controls nucleocytoplasmic transport and has multiple roles during cell division. A new study has identified the nuclear export factor Crm1 as a mitotic effector of Ran-GTP at kinetochores, where it has a role in microtubule attachment.
A recent study has shown that the Ssl1 subunit of the general transcription/DNA repair factor TFIIH contains ubiquitin ligase activity that is dependent on a RING domain. The RING domain is required for transcription of a subset of yeast genes that are involved in DNA damage repair, thus uncovering a novel ubiquitination-associated function for TFIIH in the repair process.
How cells disassemble their focal adhesions is not well understood. Now, Ezratty et al. have shown that the GTPase dynamin acts after microtubule targeting of focal adhesions to trigger their disassembly. One intriguing possibility is that dynamin might drive disassembly through endocytosis.
It has long been known that the mammalian small GTPase Rab5 is involved in clathrin-mediated endocytosis. However, most Rab5-interacting proteins are localized to endosomes rather than to the plasma membrane. A newly discovered nucleotide-exchange factor for Rab5 in Caenorhabditis elegans now provides the missing link for activating Rab5 at the plasma membrane.
Factors that determine whether precursor cells will differentiate into adipocytes remain poorly understood. A systematic evaluation of gene expression in cells with a continuum of differentiation potentials has confirmed the importance of certain pathways and has identified a novel regulator of brown adipogenesis.
