Most forms of cancer involve a step where cells move out of an epithelial layer, a step that requires the loss of the apical domain of epithelial cells. We show how this loss of polarity is regulated at multiple levels by key polarity proteins.

Farkas et al. identify monotopic hairpin proteins as novel clients of the guided entry of tail-anchored proteins (GET) pathway. They demonstrate that high efficiency GET pathway–mediated ER targeting of the budding yeast hairpin protein Erg1, a key enzyme of sterol synthesis, becomes essential under conditions requiring increased Erg1 biogenetic flux.

Ahmad and colleagues report that presynaptic accumulation of NRG3 involves multiple processes that include release of the EGF-containing domain from the TGN following BACE1 cleavage, transcytosis from somatodendritic to axonal plasma membranes, and selective retention at glutamatergic terminals through trans-synaptic interactions with postsynaptic ErbB4 receptors.

The machinery and cellular mechanisms involved in multivesicular body (MVB) biogenesis are not fully understood. Shi et al. reveal that the F-actin crosslinker FLN-2/filamin acts as a bridging molecule that docks MVB on the actin cytoskeleton to facilitate MVB biogenesis.

Abu Rmaileh et al. demonstrate that the axon guidance adaptor protein DPYSL2 is essential for promoting breast cancer cell migration. Specifically, this adaptor protein interacts with JAK1 to regulate STAT3 signaling and subsequently vimentin expression.

Vega-Lugo, da Rocha-Azevedo et al. analyze three-color microscopy images to determine whether the colocalization between two molecular entities is influenced by their colocalization with a third entity, providing evidence for cooperativity or competition between molecular interactions and for their enhancement or suppression at subcellular locations.

Ji et al. show that the autophagy proteins VMP1 and TMEM41B are required for β-coronavirus infection, and they function at different steps during DMV biogenesis. TMEM41B is involved in nsp3/4 binding and ER zippering, while VMP1 is essential for bending the paired ER into DMVs.