The local rules that control cell shape and movement are not understood. Here, Pipathsouk et al. discover a novel nanoscale organization of a key actin regulator that could explain how cellular protrusions expand and self-straighten and how transcellular holes are repaired.
The Rab7 effector WDR91 promotes autophagy-lysosome degradation in neurons by regulating lysosome fusion
How distinct Rab7 effectors coordinate to regulate lysosomal homeostasis is largely unknown. Xing et al. reveal that the Rab7 effector WDR91 competes with VPS41, another Rab7 effector, to maintain appropriate lysosomal fusion required for autophagy-lysosome degradation in neurons.
Huang et al. reveal that the microcephaly-related protein WDR62 possesses an intrinsic affinity for curved microtubules and regulates spindle dynamics by functioning as an adaptor protein between its recruiting factor TPX2/Aurora A and the effector katanin.
Guerreiro et al. show that loss of the primary microcephaly gene WDR62 in human cells mislocalizes the microtubule-severing enzyme katanin from mitotic spindle poles. This mislocalization reduces microtubule minus-end depolymerization, slowing poleward microtubule flux and promoting asynchronous chromosome segregation in anaphase.
In this study, Trela et al. delineate the cellular mechanisms governing early mammary gland development and find that its initial growth is primarily accomplished by cell migration. Moreover, they suggest that mammary bud invagination is driven by contractile cells encircling the bud—the ring cells.
Although replication stress response has been extensively studied, almost nothing is known about the replication stress response in nucleoli. Velichko et al. have studied the molecular mechanisms involved in protecting the cell from replication stress induced in rDNA (nucleolus) of the higher eukaryotes.
Abudu et al. report that mitochondrial β-barrel biogenesis protein SAMM50 recruits ATG8 proteins through an LIR motif and interacts with p62/SQSTM1 to mediate basal piecemeal mitophagy of SAM and MICOS components. Upon metabolic switch to oxidative phosphorylation, SAMM50 and p62 cooperate to mediate efficient mitophagy.
Fan et al. show that replisome disassembly during S phase is required for efficient DNA replication by recycling essential replisome components between chromatin-bound and soluble compartments.
Autoinhibition of Cnn binding to γ-TuRCs prevents ectopic microtubule nucleation and cell division defects
We show that autoinhibition regulates the binding between microtubule nucleating complexes and proteins that tether them to sites of microtubule nucleation. Failure to regulate this binding properly can lead to ectopic cytosolic microtubule nucleation and major defects during cell division.
Pitsidianaki et al. show that the mesenchymal-to-epithelial transition in the Drosophila melanogaster midgut relies both on downregulation of the EMT-transcription factor Serpent and on the secretion of a specific laminin trimer from the neighboring mesoderm.
Gupta et al. investigate forces generated during cell division in confining epithelial monolayers. In addition to finding that cells generate forces during mitotic rounding, they find that cells generate protrusive forces along the division axis that drive elongation and outward forces that facilitate postdivision spreading.
Neurons release specific signaling and pathological cargoes in membrane-bound extracellular vesicles. Walsh et al. show that cargo sorting into extracellular vesicles at presynaptic nerve terminals depends on a balance between the Alzheimer’s disease–implicated endosomal retromer complex and Rab11-mediated recycling.
SUMO homeostasis promotes error-free chromosome segregation. Quan et al. report the structure of a targeting peptide of the Ulp2 desumoylase bound to yeast Ctf3/CENP-I. Disrupting the interaction produces hyper-sumoylated kinetochores, demonstrating the existence of a conserved and dedicated pathway for the regulation of kinetochore sumoylation.
Kinetoplastids are evolutionarily divergent eukaryotes that have an unconventional set of kinetochore proteins. Marcianò et al. show that KKT2 and KKT3 play important roles in kinetochore assembly in Trypanosoma brucei. Centromere localization of these proteins is mediated by the unique centromere localization domain.
Sander et al. have parsed the lipid composition of native-source photoreceptor disks and found large differences in fatty acid unsaturation and chain length between the center and rim regions. They selectively copurified membrane proteins and lipids from each region in SMALPs using nanobodies and antibodies.
Galloni, Carra, et al. demonstrate that Arp3B isoform–specific Arp2/3 complexes generate branched actin networks with faster disassembly kinetics. This increased turnover is due to oxidation of Met293 of Arp3B by the methionine monooxygenase MICAL2, which is recruited to the branched actin network by coronin 1C.
Using high-resolution live imaging within brain slices, Coquand et al. describe the organization of the microtubule cytoskeleton in radial glial cells. They identify an acentrosomal bipolar network, generated from varicosities by CAMSAP family members. This organization is conserved in human basal radial glial cells.
Leon et al. demonstrate that the histone methyltransferase DOT1L is upregulated during oncogene-induced senescence and promotes H3K79 methylation at the IL1A locus. This leads to increased expression of downstream senescence-associated secretory phenotype (SASP) genes and is uncoupled from the cell cycle arrest.
Yang et al. applied a microfluidics-based imaging method to resolve a controversy regarding how ubiquitinated lysosome membrane proteins are sorted into the lumen for degradation. ESCRTs, but not intralumenal fragments, are responsible for the sorting.
This study shows that MYDGF regulates neutrophil behavior in response to tissue damage but not microbial cues. The findings suggest that MYDGF promotes wound healing in larval zebrafish by providing a brake on neutrophil inflammation.