On the cover
A chromosome segregation error in a human cancer cell. Elevated levels of the protein GTSE1 in cancer cells induce chromosome instability through microtubule stabilization. Blue, DNA; purple, microtubules; white, kinetochores. Image © 2016 Bendre et al.
See page 631.
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People & Ideas
Formosa and Ryan preview Qi et al.’s new insights into the structural basis of mitofusin function.
Martin Graef highlights Yamashita et al.’s finding that mitophagy can occur independently of the canonical mitochondrial fission apparatus.
Chitramuthu and Bateman highlight recent work proposing that the receptor tyrosine kinase EphA2 functions as receptor for the growth factor progranulin.
Henneberger and Steinhäuser discuss work by Shen et al. about astrocytic TLR4’s role in promoting excitatory synaptogenesis and seizure susceptibility.
Centrosomes play a key role in organizing the microtubule spindle that separates chromosomes during mitosis. Bennabi et al. review how microtubule spindle formation and chromosomal segregation also occur in oocytes during cell division by meiosis despite the absence of centrosomes.
Mitofusin 1 (MFN1) mediates mitochondrial fusion, but the mechanisms involved are unclear. Qi et al. present the crystal structures of a minimal GTPase domain of human MFN1, which suggest that MFN1 tethers apposing membranes through nucleotide-dependent dimerization.
GTSE1 tunes microtubule stability for chromosome alignment and segregation by inhibiting the microtubule depolymerase MCAK
The microtubule depolymerase MCAK influences chromosomal instability (CIN), but what controls its activity remains unclear. Bendre et al. show that GTSE1, a protein found overexpressed in tumors, regulates microtubule stability and chromosome alignment during mitosis by inhibiting MCAK. High levels of GTSE1 are linked to chromosome missegregation and CIN.
Mitochondrial division occurs concurrently with autophagosome formation but independently of Drp1 during mitophagy
It remains controversial whether Dnm1/Drp1-mediated mitochondrial division is essential for mitophagy. Yamashita et al. show that Dnm1/Drp1-independent mitochondrial division occurs after formation of isolation membranes and in cooperation with autophagosome formation during mitophagy.
The miR-103/107 family is preferentially expressed in the stem cell–enriched limbal epithelium and regulates multiple characteristics associated with stem cells. Park et al. show that miR-103/107 also contribute to limbal epithelial homeostasis by suppressing macropinocytosis and preserving end-stage autophagy.
The receptor for the growth factor progranulin has remained unclear. Neill et al. show that the Ephrin receptor tyrosine kinase EphA2 is a functional signaling receptor for progranulin and mediates its effects in capillary morphogenesis and autoregulation.
Lee et al. show that PGAP6 is a glycosylphosphatidylinositol (GPI)-specific phospholipase A2 expressed on the cell surface. PGAP6 selectively acts on a GPI anchor of CRIPTO, but not its close homologue CRYPTIC, and modulates Nodal signaling during embryonic development.
Postnatal activation of TLR4 in astrocytes promotes excitatory synaptogenesis in hippocampal neurons
Shen et al. demonstrate a developmental role of astrocytes in shaping a predisposition to seizure generation. Activation of TLR4–MyD88–ERK1/2 signaling pathway in astrocytes during a critical postnatal period promotes excitatory synapse generation, leading to enhanced seizure susceptibility.
Cadherin-6B proteolysis promotes the neural crest cell epithelial-to-mesenchymal transition through transcriptional regulation
Cadherin proteolysis reduces cell–cell adhesion and generates cleavage products that could possess independent functions. Here, Schiffmacher et al. reveal that the intracellular C-terminal fragment generated by Cadherin-6B proteolysis promotes chick cranial neural crest cell EMT through positive transcriptional feedback into the neural crest gene regulatory network.