CCT2 is an aggrephagy receptor for clearance of solid protein aggregates.

Protein aggregation is a hallmark of multiple human pathologies. Autophagy selectively degrades protein aggregates via aggrephagy. How selectivity is achieved has been elusive. Here, we identify the chaperonin subunit CCT2 as an autophagy receptor regulating the clearance of aggregation-prone proteins in the cell and the mouse brain. CCT2 associates with aggregation-prone proteins independent of cargo ubiquitination and interacts with autophagosome marker ATG8s through a non-classical VLIR motif. In addition, CCT2 regulates aggrephagy independently of the ubiquitin-binding receptors (P62, NBR1, and TAX1BP1) or chaperone-mediated autophagy. Unlike P62, NBR1, and TAX1BP1, which facilitate the clearance of protein condensates with liquidity, CCT2 specifically promotes the autophagic degradation of protein aggregates with little liquidity (solid aggregates). Furthermore, aggregation-prone protein accumulation induces the functional switch of CCT2 from a chaperone subunit to an autophagy receptor by promoting CCT2 monomer formation, which exposes the VLIR to ATG8s interaction and, therefore, enables the autophagic function.

TCF7L2 acts as a molecular switch in midbrain to control mammal vocalization through its DNA binding domain but not transcription activation domain.

Vocalization is an essential medium for social signaling in birds and mammals. Periaqueductal gray (PAG) a conserved midbrain structure is believed to be responsible for innate vocalizations, but its molecular regulation remains largely unknown. Here, through a mouse forward genetic screening we identified one of the key Wnt/ß-catenin effectors TCF7L2/TCF4 controls ultrasonic vocalization (USV) production and syllable complexity during maternal deprivation and sexual encounter. Early developmental expression of TCF7L2 in PAG excitatory neurons is necessary for the complex trait, while TCF7L2 loss reduces neuronal gene expressions and synaptic transmission in PAG. TCF7L2-mediated vocal control is independent of its ß-catenin-binding domain but dependent of its DNA binding ability. Patient mutations associated with developmental disorders, including autism spectrum disorders, disrupt the transcriptional repression effect of TCF7L2, while mice carrying those mutations display severe USV impairments. Therefore, we conclude that TCF7L2 orchestrates gene expression in midbrain to control vocal production through its DNA binding but not transcription activation domain.

In vitro adherence and invasion of primary chicken oviduct epithelial cells by Gallibacterium anatis.

Gallibacterium anatis (G. anatis) has been suggested to have a causal role in salpingitis and peritonitis in egg-laying chickens, leading to decreased egg production and increased mortality worldwide. Adherence and invasion of epithelial cells are thought to play a role in the pathogenesis of G. anatis infection. The purpose of this article was to study adherence and invasion of G. anatis using two G. anatis strains of different virulence (Yu-PDS-RZ-1-SLG strain, highly virulent and F149T strain, non-virulent) via infection of the primary chicken oviduct epithelial cells (PCOECs).The results showed that Yu-PDS-RZ-1 -SLG strain was able to attach to PCOECs at higher levels than that of F149T strain, but no invasion was observed with either strain. However, cell debris and cell apoptosis were observed after being exposed to G. anatis Yu-PDS-RZ-1-SLG for 90min, whereas G. anatis F149T did not cause cell damage, and adherence was prevented by trypsin treatment of bacterial cells. Cytokines were detected by ELISA after infection, and the results showed that the expression of IL-6, TNF-α, and IFN-γ levels was higher in virulent strain infection than that of the avirulent group. Results also indicated that the highly virulent strain G. anatis displayed an increased level of adherence. Changes in cytokine profiles in this study suggested that the production of cytokines might influence the microenvironment of oviduct and promote adherence, serving as a possible mechanism inducing cell damage.