Yamamoto highlights work from Nthiga et al. that shows that Calcoco1 binds Golgi-resident ZDHHC17 to facilitate autophagic degradation of the Golgi.
Phuyal and Farhan discuss works from Shomron et al. and Weigel et al. that provide exciting new insight to the debate about the nature of ER-to-Golgi carriers.
McClatchey highlights work from Kindberg et al. describing that EPH/EPHRIN signaling drives cell segregation through regulation of cortical actomyosin contractility.
Douanne et al. outline the multiple shared molecular mechanisms underlying two distinct biological structures, primary cilia and immune synapses.
Chen et al. show how kinetochores integrate mechanics and biochemistry using optogenetic manipulation of Aurora B kinase. Aurora B promotes microtubule depolymerization at low tension or microtubule release at high tension. Thus, tension is a signal inducing distinct error-correction pathways.
Vessoni et al. demonstrate telomere shortening leads to a unique DDR response in human pluripotent stem cells. Unlike terminally differentiated cells, telomere shortening induces formation of single-stranded DNA telomere overhangs in hPSCs, which activate ATR signaling and lead to mitotic catastrophe and p53-dependent cell death.
RNA:DNA hybrids are important intermediates in cellular processes. Smolka et al. establish controls to test the specificity of the S9.6 anti-RNA:DNA hybrid antibody in imaging approaches. They found that S9.6 immunofluorescence signal derives primarily from ribosomal RNA, not RNA:DNA hybrids.
TMEM41B and VMP1 are scramblases and regulate the distribution of cholesterol and phosphatidylserine
VMP1 and TMEM41B, integral membrane proteins of the ER, regulate the formation of autophagosomes, lipid droplets, and lipoproteins. Here, Li, Wang, et al. show that they have phospholipid scramblase activity, which is essential to the normal distribution of cholesterol and phosphatidylserine in mammalian cells.
Nthiga et al. identify CALCOCO1 as a receptor for autophagic degradation of Golgi during nutrient starvation. CALCOCO1 binds the Golgi-resident palmitoyltransferase ZDHHC17 and ATG8 family proteins to facilitate Golgiphagy to control Golgi size. Depletion of CALCOCO1 causes expansion of the Golgi and accumulation of its structural and membrane proteins.
Dello Stritto et al. provide evidence that DNA lesions in both germline mitotic and meiotic compartments are less capable of triggering apoptosis in the absence of topoisomerase 3. In topoisomerase 3 mutants, uncontrolled bloom helicase activity governs repair of defective recombination intermediates to evade apoptosis.
Aurora B switches relative strength of kinetochore–microtubule attachment modes for error correction
Doodhi et al. reconstitute the yeast kinetochore–microtubule interface in vitro and compare the relative strength of distinct kinetochore–microtubule interaction modes. Their results suggest how Aurora B kinase promotes the exchange of kinetochore–microtubule interactions to eliminate aberrant interactions and establish chromosome biorientation.
Wang et al. show that meiotic spindle assembly in Drosophila oocytes depends on the Borealin subunit of the chromosome passenger complex (CPC). Borealin does this by colocalizing with HP1, recruiting the CPC to the chromatin, and mediating movement of the CPC to the microtubules.
Correct mitotic entry requires inhibition of PP2A-B55 before nuclear envelope breakdown. This inhibition is mediated by Greatwall-phosphorylated Endosulfine. This works shows Endos and PP2A-B55 must function in the cytoplasm, which explains why nuclear Greatwall relocates to the cytoplasm in prophase.
Live-cell microscopy reveals a novel mode of function for COPII: COPII binds the membrane at the boundary between the ER and ER exit sites, where it executes cargo sorting and concentration into ERES and does not coat cargo exporting containers.
The Golgi matrix protein giantin is essential for normal skeletal formation. Here, Stevenson et al. show that it also has a role in fracture repair and is required for intracellular processing of the N-terminal propeptide of type I procollagen.
Parkin-independent mitophagy via Drp1-mediated outer membrane severing and inner membrane ubiquitination
Oshima et al. report that in the absence of Parkin activity, cells adapt to mitochondrial proteotoxicity through a Drp1-mediated mechanism that includes the severing of the OMM and IMM ubiquitination, followed by recruitment of autophagy machinery to the ubiquitinated IMM proteins.
How autophagy in neurons is regulated by synaptic activity is largely unknown. Kulkarni et al. show that synaptic activity decreases the motility and increases the degradative function of autophagic vacuoles within dendrites but not axons.
Huang et al. report a two-phase kinetic model of proinflammatory cytokine production in LPS stimulation and caspase inhibition conditions involving the activation of RIPK1 kinase to mediate sustained NF-κB activation, which may explain RIPK1-mediated inflammation in chronic human inflammatory diseases.
Rac1 promotes malignancy. Oncogenic Rac1 and its effector PAK1 disrupt junctions via internalization of cadherin adhesion receptors by bulk fluid uptake. PAK1 phosphorylates a key regulator of intracellular trafficking, RabGDIβ, thereby modulating its affinity with specific partners (i.e., Rab11) to re-route cadherin away from cell–cell contacts.
Zaman and Lombardo et al. characterize cells lacking all ERM proteins or their activating kinases. This reveals that active ERMs are local negative regulators of RhoA necessary to mediate the architecture of the apical domain.
Herrera et al. discover that Dbnl and β-catenin cooperate to promote pro-N-cadherin processing. This study shows that β-catenin and Dbnl interact with phosphorylated pro-N-cadherin in the Golgi apparatus, promoting propeptide excision and the final maturation of N-cadherin, which is critical for adherens junction (AJ) formation and for apico-basal polarity maintenance. AJs concentrate at the subapical region of neural stem cells and are critical to maintaining apico-basal polarity as these cells differentiate. Here, we show that Dbnl and β-catenin cooperate to promote pro-N-cadherin processing, facilitating AJ assembly during neural tube development.
How EPH/EPHRIN signaling regulates the biophysical properties of cells to drive tissue organization is not well understood. Kindberg et al. find that EPH/EPHRIN signaling drives cellular organization by modulating cell contact strength by regulating actomyosin contractility at heterotypic contacts.
Robertson et al. show that unlike T cells responding to conventional chemokines, T cells responding to the lipid chemoattractant S1P utilize a bleb-based mode of motility. This response involves myosin-induced increases in intracellular pressure and is directed by the cortical cytoskeletal proteins ezrin and moesin.
Phospholipase Cγ1 (PLCγ1) hydrolyzes PIP2 to generate IP3 and DAG to transduce T cell receptor (TCR) signaling. Zeng et al. show that PLCγ1 promotes phase separation of the TCR pathway by crosslinking LAT and protecting LAT from CD45-mediated dephosphorylation.
Gutiérrez et al. describe a novel function for the molecular motor KIF13A, in complex with centaurin-α1, for the insertion of AMPA receptors at synapses during long-term potentiation. This process is mediated by the remodeling of intracellular endosomal compartments in the dendritic shaft.
Dendritic spines undergo rapid size expansion upon induction of long-term potentiation. Yang et al. uncover that in response to Ca2+/calmodulin, endophilin A1 quickly associates with the plasma membrane and recruits p140Cap to promote actin polymerization that provides driving force for spine enlargement.