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The motor protein dynein binds growing microtubule ends, but how it is recruited to plus ends has not been clear. Using in vitro reconstitution and TIRF microscopy, Surrey and colleagues identify a recruitment pathway in which the plus-end binding protein EB1 binds CLIP-170, which in turn recruits the p150 dynein subunit.
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.
Cell–cell interactions, a key feature of the stem cell niche, regulate many aspects of stem cell behaviour. N-cadherin-mediated anchorage of neural stem cells within the adult neural niche maintains stem cell quiescence, and its release by the metalloproteinase MT5-MMP promotes neural stem cell activation.
Collective cell migration is characterized by the maintenance of intercellular contacts during cell movement. The maintenance of N-cadherin-based junctions during collective migration is now shown to be facilitated by their treadmilling from the cell front to the rear, followed by N-cadherin endocytosis and recycling to the leading edge.
The kinesin-4 motor protein Kif7 regulates Hedgehog signalling at cilia in mammals by controlling the activity of Gli transcription factors. Kif7 is now found to inhibit microtubule growth to restrict and coordinate the length of axonemal microtubules at the ciliary tip. Such Kif7-mediated organization of the ciliary tip compartment regulates Gli activity and is proposed to be required for correct Hedgehog signalling.
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.
Gundersen and colleagues report that the FHOD1 formin is involved in nuclear positioning, by physically linking nesprin-2G, a protein of the outer nuclear membrane, to actin cables, to allow the formation of the transmembrane actin-associated nuclear (TAN) lines that are needed to move the nucleus.