Issues

Yang and colleagues preview work from Iguchi et al. that demonstrates an important new role IKKβ in the degradation and clearance of cytoplasmic TDP-43.

Sun et al. discusses recent work from Li et al. describing a cascade of RAB regulation in unconventional trafficking of PGP-1 to the cell surface in C. elegans.

Phosphatidylserine levels and distribution are tightly controlled by dedicated enzymes at the ER and plasma membrane. Nakatsu and Kawasaki discuss new work by Aoki and colleagues, which reveals an acute reliance on phosphatidylserine synthesis in B cell lymphomas needed to prevent aberrant B cell receptor activation and ensuing apoptosis.

Sun et al. report that NuSAP regulates spindle length control and microtubule flux to ensure chromosome congression. They find that Aurora A-mediated phosphorylation of NuSAP at S240 promotes its interaction with Kif2A on the spindle body and reduces its localization on the spindle poles.

Mahone et al. use genetic, biochemical, and single-molecule imaging approaches to define a signaling pathway that coordinates chromosome segregation with progression of constriction during cell division in the bacterium Caulobacter crescentus. This pathway ensures genome integrity during the division process.

Wang et al. explore the dynamic behaviors of two chromosome axis–associated proteins, LAB-1 and LAB-2, during meiotic prophase in Caenorhabditis elegans, revealing that their recruitment senses axis differentiation. Both proteins have phase separation capacities, which may promote the establishment of distinct chromosome subdomains required for accurate chromosome segregation.

Paul et al. demonstrate that NAP1/AZI2 is a cell cycle protein that activates TBK1 during mitosis and regulates key mitotic and cytokinetic proteins to ensure accurate cell division.

The function of STK19, a protein long thought to be a kinase, has been controversial in recent studies. Here, Li et al. demonstrate that STK19 is unlikely to be a kinase but rather a DNA/RNA-binding protein involved in DNA damage repair and cell proliferation.

Lamins form a homogeneous meshwork structure under the nuclear envelope. Yamamoto-Hino et al. show that Drosophila PIGB is responsible for the homogenous lamin meshwork. In addition, the loss of PIGB changes the chromatin distribution and nuclear mechanical properties.

Proteins function within specific locations of the cell. Oftentimes their mislocalization is associated with disease. Here, we delineate a retention mechanism at nuclear pore complexes that enriches nuclear transport receptors in the nucleus to export essential cargoes out of it.

TDP-43 aggregation is a pathological feature of ALS and FTLD. This study demonstrates that the IKK complex promotes the degradation of cytoplasmic TDP-43 through proteasomes, and IKKβ is a major factor in TDP-43 degradation. IKKβ phosphorylates TDP-43 and significantly reduces the expression level and toxicity of the aggregation-prone TDP-43.

Metastatic colorectal cancer is a malignant disease with poor therapeutic outcomes. In this study, the authors reveal the carcinogenic function of XAF1 in mCRC and propose the XAF1-VCP-RNF114-JUP axis as a potential therapeutic target for CRC metastasis.

Li et al. demonstrate that activated BLK phosphorylates TOLLIP and promotes its dissociation from IRAK1 to enable efficient inflammatory response. This study uncovers uncharacterized roles of BLK in regulating TLR/IL-1R–mediated inflammatory responses and suggests the possibility of targeting this kinase for alleviation of excessive inflammation.

Rosa-Birriel et al. describe a Rho1-dependent pulsatile medioapical actomyosin network that integrates biochemical and mechanical signals, creating an adaptive supracellular actomyosin network that coordinates the mechanical behavior of neighboring cells and regulates cell shape and tissue integrity.

Omi et al. identify phosphatidylserine (PS) synthesis as a key metabolic vulnerability in B cell receptor (BCR)-positive B cell lymphomas. Inhibition of PS synthesis causes an imbalanced phospholipid metabolism via membrane contact-based lipid transfer machinery, leading to aberrant BCR hyperactivation and ultimately cell death.

Some integral membrane proteins can reach the plasma membrane in a Golgi-bypassing manner, a process also known as type IV UcPS. Here, Li et al. report that RAB-8– and RAB-11–positive endosomes are utilized as intermediate carriers in the unconventional apical protein transport.

Arnold et al. present hGRAD, a “one-fits-all” system that can be inserted in one step into any cell that expresses GFP-tagged proteins, allowing their rapid and inducible degradation. The authors show that hGRAD efficiently degrades RNA binding proteins that localize to nuclear condensates and discover a hidden function of the splicing factor SRSF5.

Jones et al. describe a new mouse model for live visualization of the basement membrane (BM) in which endogenous type IV collagen is fluorescently labeled. Live imaging BM dynamics during skin development reveals that epidermal progenitors remain attached to and deform the BM during division, rather than lose adhesion as generally thought.