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    Podosomes in a primary human macrophage are highlighted by expression of Lifeact-RFP. The cell is treated with nocodazole, inducing cell body retraction and podosome detachment. Respective video frames are given a time color code, starting with blue and ending with red. El Azzouzi et al. show that islets of the matrix metalloproteinase MT1-MMP, embedded in the plasma membrane beneath the podosome core structure, persist beyond podosome dissolution and work as memory devices for efficient reformation of podosomes.
    Image © 2016 El Azzouzi et al.
    See page 109.

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ISSN 0021-9525
EISSN 1540-8140
In this Issue

In Focus

The mevalonate pathway drives cancer metastasis and drug resistance by promoting the activation of Arf6.

People & Ideas

Schuldiner leverages high-throughput approaches to investigate novel protein functions.



Fungal and human septins can distinguish between different degrees of micron-scale curvature in cells, suggesting that this property of the septin cytoskeleton provides a cell with a mechanism to sense its local shape.


Dickson et al. find that the ER membrane lipid phosphatase Sac1 localizes to ER–plasma membrane (PM) contact sites and acts as a cellular sensor and controller of PM phosphoinositide homeostasis.

Wu et al. show that Doa1 recognizes and recruits ubiquitinated mitochondrial outer-membrane proteins to the Cdc48–proteasome degradation pathway. Doa1 deficiency sensitizes cells to mitochondrial oxidative stress.

Sigma1 receptors inhibit store-operated Ca2+ entry and reduce the Ca2+ content of the intracellular stores. These effects are regulated by Sigma1 receptor ligands. A ligand-dependent interaction between Sigma1R and STIM1 reduces STIM1 association with Orai1 channels.

The mevalonate pathway (MVP) is a metabolic pathway associated with tumor invasiveness and is known to prenylate proteins, but which prenylated proteins are critical for MVP-driven cancers is unknown. Hashimoto et al. show that MVP-driven cancers require activation of the GTPase Arf6 for invasion and that the MVP substrate Rab11 is required for Arf6 activation.

Bledzka et al. show that kindlin-2 binds actin via its F0 domain, and mutation of this site diminishes cell spreading, revealing a new mechanism by which kindlin-2 regulates cellular responses.

The authors find that matrix metalloproteinase MT1-MMP is enriched at the plasma membrane of macrophage podosomes, where it persists beyond podosome lifetime and, through binding to the subcortical actin cytoskeleton, forms subcellular signposts that facilitate podosome reformation.


The authors describe automated image and data analysis tools that reveal architectural principles of the Xenopus egg extract spindle, allow for rapid, unbiased assessment of spindle phenotypes, and can be adapted to analyze other subcellular structures such as nuclei.

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