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The retromer complex coordinates retrograde transport of cargo proteins between endosomes and the trans-Golgi network. The sorting nexin SNX3 is required for the retrograde trafficking of Wntless, but not of other retrograde cargo proteins, revealing that the cargo specificity of retromer is provided by the sorting nexins.
How the unique chromatin configuration of embryonic stem cells (ESCs) integrates inputs from exogenous stimuli to maintain pluripotency remains largely unknown. The ESC-specific ATP-dependent chromatin-remodelling (esBAF) complex maintains the accessibility of the target sites of Stat3, a leukaemia inhibitory factor (LIF) signalling effector, by preventing repressive localized polycomb-mediated trimethylation of Lys 27 of histone 3 (H3K27me3).
Regulatory mechanisms to prevent centriole overduplication during the cell cycle are not completely understood. In this issue, FBXW5 is shown to control the degradation of the centriole assembly factor HsSAS-6. Moreover, the study proposes that FBXW5 is a substrate of both PLK4 and APC/C, two established regulators of centriole duplication.
Planar cell polarity (PCP) directs the orientation of mammalian epithelial cells in the skin but it is unclear how polarity is preserved during division. A dileucine motif in the atypical cadherin Celsr1 is shown to trigger the endocytosis of PCP components in mitosis to ensure that they are distributed equally to daughter cells and recycled back to the plasma membrane after division.
The STAT3 transcription factor maintains pluripotency by preventing differentiation. A Brg1-containing chromatin-remodelling complex, esBAF, is shown to direct STAT3 to its targets across the pluripotent genome. Deletion of Brg1 leads to binding of the polycomb complex and subsequent silencing of LIF/STAT targets. Unexpectedly, Brg1 also helps the polycomb complex silence Hox genes thereby further contributing to pluripotency.
Wnt secretion is facilitated by retrograde trafficking of the Wnt receptor Wntless. Korswagen and colleagues now show that endosome-to-Golgi trafficking of Wntless depends on an alternative retromer pathway that contains SNX3 in place of the canonical retromer sorting nexins.
The ubiquitin ligase APC/C is required for the metaphase-to-anaphase transition in mitosis. Downstream of Cdk1, CUEDC2 is shown to activate the APC/C by mediating the release of the checkpoint protein Mad2 from APC/C.
N-WASP activates Arp2/3-mediated actin nucleation. N-WASP is now shown to stabilize and organize the actin cytoskeleton at cell–cell junctions through its interaction with the actin-binding protein WIRE.
How regulatory elements spatially interact with their target DNA sequences is unclear. The β-globin locus control region (LCR) is found to take part in interchromosomal interactions with a few genes controlled by shared transcription factors, and to transcriptionally upregulate β-globin mRNA in a subset of cells.
Cardiac fate choices in Ciona intestinalis depend on the CDC42-mediated formation of invasive protrusions that probe for inductive signals in the environment.
PRDM16 is known to promote the differentiation of myoblastic progenitors to brown adipocytes. The miR-193b/365 microRNAs are shown to be induced by PRDM16 and promote brown fat differentiation, as well as block myogenesis.
While separase is implicated in centrosome disjunction as well as in chromosome separation, its precise role at the centrosome has been uncertain. The proteolytic activity of separase is demonstrated to induce centriole disengagement through cleavage of cohesin.
In plants, cell growth is dependent on modifications of the cell wall. In root hairs, cell wall synthesis during tip growth is found to be mediated by the activity of cellulose synthase (CESA)-like protein CSLD3, which is present in the polarized plasma membrane.
The PtdIns(4,5)P2 5-phosphatase OCRL, mutated in Lowe syndrome, is implicated in trafficking and associates with Rab GTPases. OCRL function is now extended to cytokinesis, where it controls abscission of the intercellular bridge downstream of Rab35 through the local reduction of both PtdIns(4,5)P2 levels and actin accumulation.
During brain development, pyramidal neurons migrate from the ventricular zone to reach their final destination in the cortex. In vivo depletion experiments shows that lamellipodin, through an effect on serum response factor, determines the neuronal migration mode in the developing cortex.
Hsu and colleagues show that COPI-coated buds are a common progenitor for both vesicles and tubules. The choice between these two carriers is mediated by the opposing activities of the acyltransferase LPAAT-γ and the phospholipase cPLA2-α.
The PLK4 kinase and centrosomal protein HsSAS-6 both regulate centrosome duplication. PLK4 negatively controls an FBXW5-containing ubiquitin ligase, which targets SAS-6 for destruction to restrict centrosome re-duplication.
