Issues

The COVID-19 pandemic has created additional challenges for mid-career investigators seeking new academic opportunities. JCB asked scientists to share their experiences of uprooting their research careers and laboratories during the pandemic.

Du and Yang preview new work from the Fujimoto laboratory unveiling how seipin regulates the formation of nucleoplasmic lipid droplets.

Zhang and Ye preview work from the Li group highlighting direct recognition of transmembrane helices by a membrane ubiquitin ligase adaptor in regulated degradation of an unwanted lysine transporter.

Khan and Brandman preview work from Feder et al. that reveals that spatial regulation is built into the heat shock response in budding yeast.

Tarabykin highlights work from Kunii and colleagues demonstrating a role for a SNARE complex in the regulation of neuronal progenitor polarity.

Petit-Pedrol and Groc review the regulatory role of NMDAR nanoscale organization and surface dynamics in glutamate synapse transmission and plasticity.

Sołtysik et al. show that the inner nuclear membrane of nonhepatocytes harbors triglyceride synthesis enzymes and generates nuclear lipid droplets (LDs). Seipin knockdown increases nuclear LDs through upregulating lipin-1β transcription and increasing phosphatidic acid levels in the nucleus.

Shekhar and Hoeprich et al. show that Twinfilin bypasses the normal requirement for actin filament aging (P_i release) and drives barbed end depolymerization of newly formed filaments. This occurs even under assembly-promoting conditions, where actin monomer levels are far above the critical concentration.

Stable eukaryotic flagella can maintain their length, and many protists grow new flagella while maintaining existing flagella. Mechanisms regulating this are not well understood. Atkins et al. show that CEP164C is important for this regulation, and these findings provide key novel insights into this process.

The Hedgehog pathway can be activated by cilia-associated sterol and oxysterol lipids that bind to Smoothened. Findakly et al. identify two enzymes near the ciliary base that activate the Hedgehog pathway, shedding light on how the lipid composition of cilia is established and regulated.

Ishimoto et al. show that the SLX4–XPF complex is an early key player in the DNA damage response evoked by a nucleoprotein obstacle that interferes with DNA replication, and the SLX4–ATR axis is critical for preventing chromosome instability upon such replication stress.

Gihana et al. demonstrate that Cdc14 phosphatase activity, released from the nucleolus through the mitotic exit network, terminates the asymmetric localization of Cdc42 at the end of mitosis in budding yeast. Redistribution of Cdc42 activity between the bud and mother preserves normal cell size and mitotic spindle position.

Chi et al. report that NEDD1 facilitates initiation of both cartwheel assembly and subsequent daughter centriole biogenesis on the mother centriolar PCM by serving as a pedestal. They find that PLK4-mediated phosphorylation of NEDD1 at its S325 amino acid residue promotes NEDD1 to recruit SAS-6 to the centrosome.

Many membrane proteins are selectively ubiquitinated and degraded under specific stresses. How do ubiquitin ligases ignore membrane targets under normal conditions but then recognize them under stresses? Arines et al. identify a substrate-regulated transmembrane recognition mechanism between a lysine transporter, Ypq1, and the Ssh4–Rsp5 complex.

Wakana et al. describe a new role for SCAP, a key regulatory protein in cholesterol metabolism, in promoting Golgi PI4P turnover and the biogenesis of the TGN-derived transport carriers CARTS via interaction with the cholesterol/PI4P exchange machinery at ER–Golgi membrane contact sites.

By using a degron system, Zhang and Seemann find that acute depletion of GRASP55 and 65 does not affect Golgi stacking but indirectly compromises the integrity of the Golgi ribbon through loss of vesicle transport components.

Feder, Ali et al. reveal that spatial regulation is built into the heat shock response (HSR) in budding yeast. Heat shock triggers the J-protein Sis1 to relocalize away from the nucleoplasm. Loss of Sis1 in the nucleoplasm releases the transcription factor Hsf1 from Hsp70-mediated repression to activate the HSR.

In mechanoreceptor cells, specialized cytoskeletons are formed at the site of mechanotransduction. Sun et al. reconstruct the microtubule-based cytoskeleton in fly campaniform mechanosensory cilia using electron microscopic tomography and establish dual functions for katanin p60-like 1 in shaping the cytoskeleton.

Hedgehog (Hh) is an essential signaling pathway for embryonic development and adulthood. Here, we show that noncanonical Hh induces the formation of primary cilia, the critical signaling hubs whose absence leads to a variety of severe disorders, via two distinct, critical pathways.

Fukuda et al. demonstrate that the RNA-binding protein SFPQ is preferentially transported by KIF5A rather than other motors of the kinesin-1 family. Defective axonal transport of SPFQ by KIF5A leads to axon degeneration and therefore provides a mechanistic understanding of specificity for neurologic diseases linked to the KIF5A gene.

Kunii et al. show that neuron-specific SNAP23 knockout mice lack a hippocampus and cerebellum. The SNAP23–VAMP8–Syntaxin1B complex mediates the apical localization of N-cadherin, which is essential for the formation of apical junctional complexes and the polarization of radial glial cells.

The APEX2 proximity ligation method can identify RNA, protein, and DNA interacting with or in proximity to the nuclear lamina. This work suggests a potential regulation of mRNAs containing long 3′ UTRs and uncovers variation in lamina-associated chromatin domains during the cell cycle.