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Clathrin-mediated endocytosis is an essential cellular pathway that enables signaling and recycling of transmembrane proteins and lipids. During endocytosis, dozens of cytosolic proteins come together at the plasma membrane, assembling into a highly interconnected network that drives endocytic vesicle biogenesis. Recently, multiple groups have reported that early endocytic proteins form flexible condensates, which provide a platform for efficient assembly of endocytic vesicles. Given the importance of this network in the dynamics of endocytosis, how might cells regulate its stability? Many receptors and endocytic proteins are ubiquitylated, while early endocytic proteins such as Eps15 contain ubiquitin-interacting motifs. Therefore, we examined the influence of ubiquitin on the stability of the early endocytic protein network. In vitro, we found that recruitment of small amounts of polyubiquitin dramatically increased the stability of Eps15 condensates, suggesting that ubiquitylation could nucleate endocytic assemblies. In live cell imaging experiments, a version of Eps15 that lacked the ubiquitin-interacting motif failed to rescue defects in endocytic initiation created by Eps15 knockout. Furthermore, fusion of Eps15 to a deubiquitylase enzyme destabilized nascent endocytic sites within minutes. In both in vitro and live cell settings, dynamic exchange of Eps15 proteins, a measure of protein network stability, was decreased by Eps15-ubiquitin interactions and increased by loss of ubiquitin. These results collectively suggest that ubiquitylation drives assembly of the flexible protein network responsible for catalyzing endocytic events. More broadly, this work illustrates a biophysical mechanism by which ubiquitylated transmembrane proteins at the plasma membrane could regulate the efficiency of endocytic internalization.

 

The cosmological inflow of a galaxy is speculated to be able to enter the galaxy and enhance the star formation rate (SFR) and black hole accretion rate (BHAR). In this paper, by performing high-resolution hydrodynamic simulations in the framework of macer, we investigate the fate of the inflow and its impacts on the evolution of a massive elliptical galaxy. The inflow properties are adopted from the cosmological simulation IllustrisTNG. We find that the inflow gas hardly enters but is blocked beyond ∼20 kpc from the central galaxy and becomes part of the circumgalactic medium (CGM). The gas pressure gradient, mainly contributed by the thermalized stellar wind and subdominant contributed by the energy input from the active galactic nuclei (AGNs), balances gravity and prevents the inflow from entering the galaxy. The SFR and BHAR are almost not affected by the normal inflow. However, if the rate of cosmological inflow were increased by a factor of 3, a small fraction of the inflow would enter the galaxy and contribute about 10 per cent of the gas in the galaxy. In this case, the gas density in the galaxy would increase by a factor of $\gtrsim$20. This increase is not because of the additional gas supply by the inflow but due to the increase of gas density and pressure in the CGM caused by the inflow. Consequently, the SFR and BHAR would increase by a factor of ∼5 and ∼1000, respectively. Finally, AGN feedback can perturb the motion of the inflow and heat the CGM through its intermittent outbursts.

 

We perform high-resolution hydrodynamical simulations using the framework of MACER to investigate supermassive black hole (SMBH) feeding and feedback in a massive compact galaxy, which has a small effective radius but a large stellar mass, with a simulation duration of 10 Gyr. We compare the results with a reference galaxy with a similar stellar mass but a less concentrated stellar density distribution, as typically found in local elliptical galaxies. We find that about 10 per cent of the time, the compact galaxy develops multiphase gas within a few kpc, but the accretion flow through the inner boundary below the Bondi radius is always a single phase. The inflow rate in the compact galaxy is several times larger than in the reference galaxy, mainly due to the higher gas density caused by the more compact stellar distribution. Such a higher inflow rate results in stronger SMBH feeding and feedback and a larger fountain-like inflow-outflow structure. Compared to the reference galaxy, the star formation rate in the compact galaxy is roughly two orders of magnitude higher but is still low enough to be considered quiescent. Over the whole evolution period, the black hole mass grows by ∼50 per cent in the compact galaxy, much larger than the value of ∼ 3 per cent in the reference galaxy.

 

A set of design rules reveals how disordered proteins can impact membrane curvature. 

Abstract An important parameter in the theory of hot accretion flows around black holes is δ , which describes the fraction of “viscously” dissipated energy in the accretion flow that goes directly into heating electrons. For a given mass accretion rate, the radiative efficiency of a hot accretion flow is determined by δ . Unfortunately, the value of δ is hard to determine from first principles. The recent Event Horizon Telescope Collaboration (EHTC) results on M87* and Sgr A* provide us with a different way of constraining δ . By combining the mass accretion rates in M87* and Sgr A* estimated by the EHTC with the measured bolometric luminosities of the two sources, we derive good constraints on the radiative efficiencies of the respective accretion flows. In parallel, we use a theoretical model of hot magnetically arrested disks (MADs) to calculate the expected radiative efficiency as a function of δ (and accretion rate). By comparing the EHTC-derived radiative efficiencies with the theoretical results from MAD models, we find that Sgr A* requires δ ≳ 0.3. A similar comparison in the case of M87* gives inconclusive results as there is still a large uncertainty in the accretion rate in this source. 

Clathrin-mediated endocytosis is essential for the removal of transmembrane proteins from the plasma membrane in all eukaryotic cells. Many transmembrane proteins are glycosylated. These proteins collectively comprise the glycocalyx, a sugar-rich layer at the cell surface, which is responsible for intercellular adhesion and recognition. Previous work has suggested that glycosylation of transmembrane proteins reduces their removal from the plasma membrane by endocytosis. However, the mechanism responsible for this effect remains unknown. To study the impact of glycosylation on endocytosis, we replaced the ectodomain of the transferrin receptor, a well-studied transmembrane protein that undergoes clathrin-mediated endocytosis, with the ectodomain of MUC1, which is highly glycosylated. When we expressed this transmembrane fusion protein in mammalian epithelial cells, we found that its recruitment to endocytic structures was substantially reduced in comparison to a version of the protein that lacked the MUC1 ectodomain. This reduction could not be explained by a loss of mobility on the cell surface or changes in endocytic dynamics. Instead, we found that the bulky MUC1 ectodomain presented a steric barrier to endocytosis. Specifically, the peptide backbone of the ectodomain and its glycosylation each made steric contributions, which drove comparable reductions in endocytosis. These results suggest that glycosylation constitutes a biophysical signal for retention of transmembrane proteins at the plasma membrane. This mechanism could be modulated in multiple disease states that exploit the glycocalyx, from cancer to atherosclerosis. 

Streams of intergalactic gas enriched by previous star formation were observed spiraling toward a massive galaxy. 

Despite recent advances in phylogenomics, the early evolution of the largest bee family, Apidae, remains uncertain, hindering efforts to understand the history of Apidae and establish a robust comparative framework. Confirming the position of Anthophorinae—a diverse, globally distributed lineage of apid bees—has been particularly problematic, with the subfamily recovered in various conflicting positions, including as sister to all other Apidae or to the cleptoparasitic Nomadinae. We aimed to resolve relationships in Apidae and Anthophorinae by combining dense taxon sampling, with rigorous phylogenomic analysis of a dataset consisting of ultraconserved elements (UCEs) acquired from multiple sources, including low-coverage genomes. Across a diverse set of analyses, including both concatenation and species tree approaches, and numerous permutations designed to account for systematic biases, Anthophorinae was consistently recovered as the sister group to all remaining Apidae, with Nomadinae sister to (Apinae, [Xylocopinae, Eucerinae]). However, several alternative support metrics (concordance factors, quartet sampling, and gene genealogy interrogation) indicate that this result should be treated with caution. Within Anthophorinae, all genera were recovered as monophyletic, following synonymization of Varthemapistra with Habrophorula. Our results demonstrate the value of dense taxon sampling in bee phylogenomics research and how implementing diverse analytical strategies is important for fully evaluating results at difficult nodes.

 

Abstract Misalignment between rotation and magnetic fields has been suggested to be one type of physical mechanism that can ease the effects of magnetic braking during the collapse of cloud cores leading to the formation of protostellar disks. However, its essential factors are poorly understood. Therefore, we perform a more detailed analysis of the physics involved. We analyze existing simulation data to measure the system torques, mass accretion rates, and Toomre Q parameters. We also examine the presence of shocks in the system. While advective torques are generally the strongest, we find that magnetic and gravitational torques can play substantial roles in how angular momentum is transferred during the disk formation process. Magnetic torques can shape the accretion flows, creating two-armed magnetized inflow spirals aligned with the magnetic field. We find evidence of an accretion shock that is aligned according to the spiral structure of the system. Inclusion of ambipolar diffusion as explored in this work has shown a slight influence in the small-scale structures but not in the main morphology. We discuss potential candidate systems where some of these phenomena could be present.