Issues

Sixt and Huttenlocher commemorate the life of Zena Werb.

Meroni and Vindigni preview work from the Penengo laboratory describing a new role for the interferon-stimulated gene ISG15 in DNA replication control.

Arora and Olkkonen discuss a recent study from Pedersen et al. on the role of Protrudin in cancer cell invasion.

Brian Pierchala previews work from Ko and colleagues, which shows that neuroinflammation can induce a non-canonical necroptosis pathway leading to SARM1-mediated axonal degeneration.

Houston et al. synthesize recent work analyzing Mad1–cyclin B1 complex function in mitosis.

In this review, Acoba et al. discuss the surprisingly complicated mechanisms, regulation, and functions of mitochondrial membrane building.

Zhang and colleagues summarize phase separation and transition in the assembly of autophagosome formation sites and triage of protein condensates for degradation.

Raso et al. find that high levels of interferon-stimulated gene 15 (ISG15), which is very frequent in cancer and robustly induced by pathogen infection, accelerate DNA replication fork progression, impacting genome stability and response to chemotherapy.

To segregate chromosomes, the mammalian spindle must generate and respond to force. How it does so remains poorly understood. Pulling on the spindle using microneedles, Long et al. show that it can locally dissipate sustained force by regulating microtubule dynamics and breakage, thereby preserving global spindle structure.

TAN1 is a microtubule-binding protein required for the spatial control of plant division plane orientation. TAN1 mediates both lateral and end-on microtubule interactions in vitro. These activities may promote proper division plane orientation in vivo.

Magliozzi et al. show that fission yeast cell polarity kinase Pak1 regulates cytokinesis. Through a phosphoproteomic screen and subsequent mutant analysis, their work uncovers direct targets and mechanisms for Pak1 activity during cell division.

Sas4 is a conserved basal body assembly protein. Here, Ruehle et al. describe a previously unknown link between basal bodies and the control of cell division by Hippo signaling molecules that depends on Sas4.

The small Rho GTPase Cdc42 is a well-known regulator of cytoskeletal rearrangement and polarity development in all eukaryotic cell types. Here, Lu and Drubin report the serendipitous discovery of a novel Cdc42-ESCRT–nuclear envelope/endoplasmic reticulum connection.

Rsp5 is an E3 ubiquitin ligase of the Nedd4 family that regulates many cellular processes in yeast. Zhu et al. show that two paralogous Rsp5 adaptors, Rcr1 and Rcr2, are sorted to distinct locations. Exomer sorts Rcr1 to the plasma membrane via a new sorting motif, and the upregulation of Rcr1 via the calcineurin/Crz1 signaling pathway maintains cell integrity.

Panda et al. find that Rcd4 is required for centriole duplication and ciliogenesis in neurosensory organs but dispensable for spermatogenesis, indicating tissue specific requirements for centriole formation. Loading of Rcd4 and its binding partner Ana3 onto daughter centrioles is a prerequisite for the mitotic conversion of centrioles into centrosomes.

Moon et al., demonstrate a new role for ribosome-associated quality control (RQC) factors in mediating mRNA release from ribosomes during stress to promote their localization to stress granules.

Begovich et al. identify 17 metabolic enzymes that are stress-specific components of yeast stress granules (SGs). The product of one of these enzymes, AdoMet, is an evolutionarily conserved regulator of SG assembly and blocks the recruitment of pathogenic TDP-43 into SGs in ALS models, highlighting its therapeutic potential.

CDKA;1, the Arabidopsis orthologue of Cdk1 and Cdk2, controls microtubule organization in meiosis. Sofroni et al. find that reducing CDKA;1 activity converts simultaneous cytokinesis—the separation of all four meiotic products concomitantly—into two successive cytokineses after the first and second meiotic divisions, as found in many crop species.

Chapa-y-Lazo et al. report that, during anaphase, astral microtubules and dynein remove myosin from the non-equatorial cell cortex and trigger a bidirectional cortical flow toward the equator, which facilitates assembly of the actomyosin contractile ring.

Chen et al. identified a bipartite motif from the 440-kD giant ankyrin-B, which bundles and avidly binds to microtubules in vitro. They further demonstrated that giant ankyrin-B suppresses axon collateral branching and prevents microtubule invasion of nascent axon branches through direct interaction with microtubules.

In this article, Osseni et al. show that by controlling acetylation of microtubules at neuromuscular junctions, HDAC6 regulates the insertion and removal of acetylcholine receptors. Accordingly, these findings provide key novel insights into the mechanisms involved in the stability and structure of neuromuscular junctions.

How lysosomes change their numbers for cell division is unknown. Yin et al. reveal that lysosome numbers increase in the S and G2/M phases in the cell cycle and the cyclin-dependent kinases CDK4/6 regulate lysosome biogenesis through TFEB/TFE3.

Autophagosomes engulf a variety of targets, from a portion of cytosol to large organelles, by regulating the size of the autophagosomal membrane. Yamamoto et al. identify ERdj8, a novel ER membrane protein that affects the size of autophagosomes.

Cancer cell dissemination is facilitated by small actin-rich plasma membrane protrusions called invadopodia. Pedersen et al. now show that invadopodia maturation and function depend on contact site formation between the endoplasmic reticulum and late endosomes, which promotes translocation of the latter to growing invadopodia.

Trafficking of matrix metalloproteinases (MMPs) through the Golgi remains enigmatic in the field. Pacheco-Fernandez et al. find that nucleobindin-1 (NUCB1), a cis-Golgi localized Ca²⁺-binding protein, plays a major role in this process by binding to MMPs, regulating their intra-Golgi trafficking, and thereby modulating cell invasion and matrix degradation.

Ko et al. demonstrate that SARM1 is required for loss of axons and neurons in a neuroinflammatory model of glaucoma. Neuroinflammatory signaling induces an axonal necroptosis that triggers SARM1-dependent axon degeneration. These findings delineate unexpected molecular and functional relationships among neuroinflammation, necroptosis, and axon degeneration.

Chastney et al. use multiplexed proximity-dependent labeling to define the topology of integrin adhesion complexes. The data support current models of adhesome architecture and provide a resource to examine proximal relationships within the adhesome and to identify novel interactors.