Issues

Aguilera-Romero and Muñiz preview work from the Kinoshita lab, which reveals that certain GPI anchor signal sequences and ER-resident protein ARV1 function together to upregulate GPI biosynthesis.

Jipa and Juhász preview results from the lab of Tao Wang which show a surprising antagonism between two branches of the unfolded protein response that dictates disease progression in a model of autosomal dominant retinitis pigmentosa.

Kournoutis and Johansen preview work from Jiménez-Moreno and colleagues, which shows that LMX1B binds to the Atg8 family member LC3B to regulate the transcription of autophagy- and cell stress–related genes potentially modulating dopaminergic cell survival.

Naghavi previews work from Mascarau et al. identifying that heterotypic cell fusion mediates the transfer of HIV-1 from infected T cells to M2 polarized macrophages.

Maiato and Silva discuss the origin and fate of chromosome segregation errors that satisfy the spindle assembly checkpoint, focusing on anaphase surveillance/correction mechanisms and post-mitotic clearance pathways.

Gallego-Paez et al. identify a previously unannotated cassette exon in the TLN1 gene that alters the mechanical properties of the talin-1 protein. This novel exon can be readily detected in many healthy tissues including skin and pancreas, and is significantly enriched in certain cancer subtypes.

Moore et al. identify a new role for the ubiquitin ligase RFWD3 in promoting replication fork reversal. They demonstrate that RFWD3 promotes recruitment of the DNA translocase ZRANB3 to stalled replication forks by inducing polyubiquitination of PCNA and interaction with ZRANB3.

Chromosome alignment and segregation in mitosis are tightly regulated. This study shows that PP6 limits the activity of Aurora A toward the kinetochore protein NDC80. NDC80 phosphorylation by Aurora A is restricted to microtubule-attached, checkpoint-silenced kinetochores and is important for regulation of both spindle size and chromosome segregation.

Dynein-driven chromosome movement facilitates chromosome synapsis in prophase I of meiosis, which is essential for genetic exchange and completion of meiosis. Dynein-1 is recruited by KASH5 in the outer nuclear envelope. The authors show that KASH5 is an activating dynein adaptor and characterize the KASH5–dynein interaction.

Liu et al. show that precursors of specific GPI-anchored proteins, such as CD55, function with an ER-resident lipid homeostasis regulator ARV1 to upregulate GPI biosynthesis in the ER. This may be an important mechanism to increase GPI when needed.

Wang et al. report that nucleus-derived CBP and SIRT7 constitute a regulatory circuit to initiate ER-phagy as an early response to ER stress. Next, they presented a model of sequential acetylation-phosphorylation to depict how ER-phagy receptor integrates divergent signals for spatiotemporal control of ER homeostasis.

Mutations in rhodopsin are the major cause of autosomal dominant retinitis pigmentosa. Zhao et al. demonstrated that PERK signaling plays key roles in maintaining rhodopsin homeostasis through attenuating IRE1-induced autophagy, and upregulation of PERK prevents autophagy and suppresses retinal degeneration.

Using kinetic trafficking assays, genetics, and secretomics, Pereira, Stalder et al. demonstrate the role of the exocyst complex in the secretory pathway. Exocyst subunits co-localize with post-Golgi carriers and their abrogation results in intracellular cargo accumulation in various cell types.

Jiménez-Moreno et al. demonstrate that human ATG8 proteins stimulate transcriptional cell stress protection via binding to the LMX1B transcription factor, an essential determinant of dopaminergic neuronal development and maintenance in the adult brain.

Limar et al. show that the yeast protein Svf1 localizes to the cis Golgi apparatus via an N-terminal amphipathic helix. Svf1 directly binds ceramides and is necessary to maintain appropriate levels of complex sphingolipids, most likely by transporting ceramides between the ER and the Golgi apparatus.

Liu et al. identify that the endothelium-derived fibronectin production regulated by Atg7 is required for the astrocytes attachment to microvascular wall. Endothelial Atg7 deficiency suppresses fibronectin via PKA/CREB signaling. This study uncovers the autophagy-independent function of endothelial Atg7 in the maintenance of the BBB integrity.

Fulford et al. show the cell adhesion molecule Fat regulates Expanded by direct binding, stabilizing, and localizing Expanded. Highly conserved regions of Fat bind Expanded and are needed to control tissue growth in vivo. Fat–Dachsous binding can occur via direct cytoplasmic interactions as well as previously described extracellular interactions.

Mascarau et al. demonstrate the relevance of HIV-1 infection of tissue-resident macrophages by fusion with infected CD4⁺ T cells and show that this process is modulated by the macrophage activation state and is under the control of the CD81/RhoA/Myosin axis.

Parker et al. show that the Ena/VASP protein, EVL, complexes with the I-BAR protein, MIM/MTSS1, to drive filopodial protrusion from dendrites during neurodevelopment. These dendritic filopodia are precursors of dendritic spines and are critical for guiding neural connectivity. The findings presented here further our understanding of neural plasticity, which is compromised in several neurodevelopmental disorders.

Jansen et al. introduce StableMARK (Stable Microtubule-Associated Rigor-Kinesin), a live-cell marker to visualize stable microtubules. This live-cell marker enables the exploration of different MT subsets throughout the cell cycle to understand how they contribute to cellular organization and transport.

Spatial and temporal discontinuities in time-lapse movies frequently disrupt automation methods such as 3D object segmentation and object tracking. To overcome this hurdle, we introduced SpinX, an image analysis framework to combine deep learning and mathematical object modeling to track mitotic spindle movements in 3D.

Simon et al. present ExTrack, a tool to characterize single molecules from single-particle tracking. Using a probabilistic approach, ExTrack accurately characterizes different motion states, extracts state-duration histograms, and estimates single-molecule states, even in previously intractable cases of high noise and frequent state transitions.