Articles in 2014

The ovary surface epithelium undergoes ovulation-induced tear and remodelling. Barker and colleagues have identified Lgr5-expressing stem cells in the mouse ovary and show that they contribute to ovary organogenesis as well as participate in epithelial repair throughout life.

Chromosomal instability (CIN) is a common feature of colorectal cancer cells and several mechanisms have been suggested for CIN generation. Bastians and colleagues find that increased microtubule plus-end stability can be triggered by AURKA overexpression and is associated with abnormal spindles and lagging chromosomes in colorectal cancer cells.

How microtubule minus ends are organized during spindle assembly has remained unclear. Lecland and Lüders demonstrate that γ-tubulin ring complexes associate with non-centrosomal minus ends, and that minus ends are transported towards spindle poles in a manner dependent on the microtubule motors dynein, HSET and Eg5.

Anderson and colleagues report that the kinesin-4 family member Kif7 binds to microtubule plus ends at cilium tips to regulate their length and structure, and to ensure the fidelity of Hedgehog signalling.

Batlle and colleagues explore the mechanisms controlling colorectal cancer initiation. They show that GATA6 promotes adenoma stem cell self-renewal and tumour formation by inhibiting BMP signalling.

Understanding how adhesion to the niche influences the behaviour of neural stem cells (NSCs) would contribute to our knowledge of tissue renewal. Farinas and colleagues have found that a metalloprotease sheds the N-cadherin ectodomain in the niche and that this participates in the activation of NSC generation and identity.

The Raf-1 kinase is important for mitogenic MAPK signalling but also inhibits pro-apoptotic Hippo signalling. Kolch and colleagues have found that the Hippo kinase LATS1 phosphorylates Raf-1 in a feedback regulatory loop to inhibit both pathways, and demonstrate by experiments and modelling that competing protein interaction can form the basis for a switch-like transition between signalling pathways.

Etienne-Manneville and colleagues demonstrate that the adherens junctions of adjacent migrating cultured cells exhibit retrograde flow along the lateral cell sides. They show that the rearward treadmilling of junctions is followed by N-cadherin endocytosis at the cell rear and anterograde trafficking to support formation of new junctional complexes at the cell front.

De Camilli and colleagues reveal that reducing cholesterol or sphingomyelin causes formation of tubular structures resembling early endocytic intermediates at the plasma membrane. These structures recruit sphingosine kinase 1 (SPHK1). Depleting SPHK1 inhibits endocytic recycling, revealing a link between sphingosine metabolism and endocytosis.

Gomis and colleagues report on the mechanisms driving colon cancer metastasis. They show that whereas ERK2 activity promotes colon cancer metastasis to the liver, reduced p38 signalling upregulates the PTHLH cytokine to allow liver metastatic cell extravasation and colonization of the lung.

It has been unclear at which stage of mouse development embryonic stem cells can be derived. Nichols and colleagues use single-cell cultures to demonstrate that derivation of cells able to proliferate without ERK signalling (a characteristic of ESCs) is limited to the early pre-implantation epiblast and is favoured by culture on a laminin substrate.

The Par polarity proteins are involved in regulating asymmetric division in stem cells in the fly. Macara and colleagues identify a PAR3 homologue that is expressed in multipotent stem cells in terminal end buds of the murine mammary gland, and is necessary for stem cell maintenance through its effect on Lkb1 kinase activity.

Thiery, Viasnoff and colleagues study the roles of myosin contractility and actin dynamics in regulating the recruitment of E-cadherin at adherens junctions, using an assay that allows live 3D imaging of the intercellular contact of a suspended cell doublet.

Wittmann and colleagues demonstrate that the turnover of mature focal adhesions is regulated by CLASP proteins. They show that CLASP recruitment to focal adhesions is involved in localized exocytosis and extracellular matrix degradation, suggesting that local matrix metalloprotease secretion might promote focal adhesion disassembly.

Hodgson and colleagues use a Rac1 biosensor to delineate a signalling pathway that promotes invadopodia dissolution through the activities of the Rac1 GEF Trio, Rac1 and the Pak1 kinase.

Many cell surface receptors are internalized by clathrin-independent endocytosis, but how clathrin-independent carriers (CLICs) are generated at the plasma membrane remained unclear. Johannes and colleagues now report that galectin-3 (Gal3) binds to glycosylated cargo proteins and glycosphingolipids. These interactions induce membrane deformation, revealing a mechanism for CLIC biogenesis.

In the presence of incorrectly segregated chromosomes, the Aurora-B-dependent abscission checkpoint prevents the final stage of cytokinesis. Stenmark and colleagues identify a role for the previously uncharacterized protein ANCHR at the checkpoint, where it acts in an Aurora-B-dependent manner to retain the ATPase VPS4 at the midbody.

Nam and van Deursen find that overexpression of either cyclin B1 or cyclin B2 in mice causes tumorigenesis and aneuploidy. They show that increased levels of these proteins lead to distinct chromosome segregation defects, and they identify a role for cyclin B2 in centrosome separation.

Cheresh and colleagues delineate a pathway that regulates tumour cell stemness and resistance to therapy. They find that the unliganded integrin α_vβ₃ is able to promote cancer cell self-renewal, tumour initiation and resistance to EGFR inhibitors by binding KRAS and RalB to activate the NF-κB pathway.

The E2-like enzyme Atg3 conjugates phosphatidylethanolamine (PE) to Atg8 to facilitate its membrane association and promote autophagosome maturation. Melia and colleagues report that Atg3 preferentially associates in vitro with highly curved, PE-enriched membranes, such as the isolation membrane of a nascent autophagosome, thus ensuring access to a local supply of PE.