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JCB asks early career investigators to share their experience launching a lab during the COVID-19 pandemic.

Spotlights

Carty and Dunleavy preview work from Murillo-Pineda et al., which describes and characterizes an experimentally generated functional human neocentromere, confirming the epigenetic nature of the event.

Köhler previews new work from the Lusk laboratory identifying a role for the lipid phosphatidic acid in recruiting the ESCRT protein Chm7 to nuclear envelope defects.

Merdes previews two studies (Wieczorek et al. and Zimmermann et al.) revealing the γ-TuRC complex structure and elucidating microtubule nucleation mechanisms.

Reviews

Reinisch and Prinz review the emerging understanding of the mechanisms, regulation, and functions of nonvesicular lipid transport in eukaryotic cells.

Reports

Murillo-Pineda et al. report a chromosome engineering system for human neocentromere formation and characterize the first experimentally generated human neocentromere. Neocentromere formation promotes local H3K9me3 eviction and cohesin and RNA polymerase II recruitment. Long-term culture results in gradual maturation of the inner centromere.

Thaller et al. demonstrate that direct binding between phosphatidic acid (PA) and the ESCRT Chm7 is required for nuclear envelope surveillance; PA also accumulates at nuclear envelope herniations. Thus, tight control of PA metabolism is required for nuclear envelope homeostasis.

Microtubule attachments to spindle poles in yeast are flexible, which allows the microtubules to pivot. Fong et al. directly measure the pivoting flexibility of the microtubule–pole interface and show that this flexibility is important for timely pole separation during mitosis.

Wieczorek et al. reconstitute the human γ-TuRC using recombinant proteins and examine the contribution of a key structural feature, the lumenal bridge, on the structure and microtubule-nucleating activity of this essential complex.

Clancy et al. develop a specific chemical inhibitor of USP9X and characterize its effects upon the cellular proteome. This analysis reveals a central role in the regulation of ribosomal stalling through control of critical E3 ligases.

Orii et al. show that phospholipids distribute symmetrically in the yeast autophagosomal membranes. They also show that de novo–synthesized phosphatidylcholine is incorporated to autophagosomal membranes preferentially and attains the symmetrical distribution within 30 min after synthesis by an Atg9-dependent manner.

Articles

In Special Collection:
Immune Cell Biology 2021

Dong et al. show that the epigenetic regulator Brd4 forms a complex with transcription factors IRF8/PU.1 to activate the transcription of NLRC4 inflammasome component Naips in macrophages. Brd4-dependent inflammasome activation protects mice from Salmonella infection via cytokine release and pyroptosis.

Ito et al. revealed that centrosomal proteins Cep57 and Cep57L1 cooperatively maintain centriole engagement during interphase in human cells. Codepletion of Cep57 and Cep57L1 induces precocious centriole disengagement in interphase, which results in centriole reduplication, centriole amplification, and chromosome segregation errors.

Rüthnick et al. decipher how the assembly of the daughter spindle pole body (dSPB) works on a molecular level. Recruitment of the proteins Spc29 and Spc42 to the N-terminus of the bridge protein Sfi1 facilitated by centrin initiates dSPB assembly.

The function of the contractile ring during cytokinesis depends on its molecular organization. This study uses single-molecule localization microscopy in live fission yeast cells to show that distinct molecular organizations of the myosin-II Myo2p correlate with different constriction rates of the contractile ring.

Stress granules are biomolecular condensates of nontranslating mRNAs and diverse proteins. Yahya et al. uncover a mutual-inhibition system between stress granules and the cyclin-dependent kinase, whereby Cdks regulate SG dynamics and SGs contribute to inhibiting cyclin transcript translation.

The molecular mechanisms that control the early events of adipogenesis are not yet fully elucidated. Audano et al. show that Zc3h10 is a proadipogenic factor essential to achieve protein synthesis repression and for proper remodeling of filamentous actin to provide a functional population of mitochondria to support the adipogenic program.

Mutations in ANO5 cause a limb-girdle muscular dystrophy characterized by membrane repair defects that make muscles more susceptible to permanent damage from normal use. This work links failed membrane repair in ANO5-deficient muscle to altered trafficking of the annexins, crucial repair proteins.

Work and Brandman measure how the ubiquitin-proteasome system (UPS) adapts to different types of stressors. They find that the UPS can adapt almost perfectly to stress conditions, even those that stabilize misfolded proteins through aggregation rather than increasing UPS substrate load.

We integrated quantitative nanoscale lipid mapping with molecular dynamic simulations to define the lipid profile within caveolae. Caveolin-1 and cavin1 individually sort distinct plasma membrane lipids. Intact caveolae containing both caveolin-1 and cavin1 further generate a distinct lipid profile, with headgroup and acyl chain selectivity.

During T cell development, genomic rearrangement must create a T cell receptor capable of transmitting signals. Allam et al. show that passage through the β-selection checkpoint requires the assembly of a platform to support TCR signaling, similar to the mature T cell immunological synapse.

Tools

Freibaum, Messing, et al. present a system that permits high-fidelity reconstitution of stress granules and the granular component of nucleoli in mammalian cellular lysate. This system permits a variety of membraneless organelle studies, including the development of therapeutics that modify properties of specific condensates.

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