Reviews & Analysis

How proteins exit the Golgi apparatus on their way to the plasma membrane is poorly understood. Protein kinase D (PKD) is known to regulate this process, but its downstream targets have remained elusive. New work now identifies a previously known player in Golgi dynamics — phosphatidylinositol 4-kinase IIIβ — as a physiological PKD substrate.

Myosin-V transports intracellular cargo along an actin filament, using a 'hand-over-hand' mechanism that moves it forward in 36-nm steps before dissociating. To achieve long run lengths, the stepping of the two myosin heads must be coordinated. Recent evidence favours the idea that this coordination is achieved by intramolecular strain between the heads, so that myosin prefers to pick up its trailing head first to search for a new actin-binding site, and move cargo forward on the actin.

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.