KANK1 shapes focal adhesions by orchestrating protein binding, mechanical force sensing, and phase separation.

Focal adhesions (FAs) are dynamic protein assemblies that connect cytoskeletons to the extracellular matrix and are crucial for cell adhesion and migration. KANKs are scaffold proteins that encircle FAs and act as key regulators of FA dynamics, but the molecular mechanism underlying their specified localization and functions remains poorly understood. Here, we determine the KANK1 structures in complex with talin and liprin-ß, respectively. These structures, combined with our biochemical and cellular analyses, demonstrate how KANK1 scaffolds the FA core and associated proteins to modulate the FA shape in response to mechanical force. Additionally, we find that KANK1 undergoes liquid-liquid phase separation (LLPS), which is important for its localization at the FA edge and cytoskeleton connections to FAs. Our findings not only indicate the molecular basis of KANKs in bridging the core and periphery of FAs but also provide insights into the LLPS-mediated dynamic regulation of FA morphology.

Repeated, Intermittent Social Defeat across the Entire Juvenile Period Resulted in Behavioral, Physiological, Hormonal, Immunological, and Neurochemical Alterations in Young Adult Male Golden Hamsters.

The developing brain is vulnerable to social defeat during the juvenile period. As complements of human studies, animal models of social defeat provide a straightforward approach to investigating the functional and neurobiological consequences of social defeats. Taking advantage of agonist behavior and social defeat in male golden hamster, a set of 6 experiments was conducted to investigate the consequences at multiple levels in young adulthood resulting from repeated, intermittent social defeats or "social threats" across the entire juvenile period. Male hamsters at postnatal day 28 (P28) were randomly assigned to either the social defeat, "social threat", or arena control group, and they correspondingly received a series of nine social interaction trials (i.e., either social defeat, "social threat", or arena control conditions) from P33 to P66. At the behavioral level (Experiment 1), we found that repeated social defeats (but not "social threats") significantly impacted locomotor activity in the familiar context and social interaction in the familiar/unfamiliar social contexts. At the physiological and hormonal levels (Experiments 2 and 3), repeated social defeat significantly enhanced the cortisol and norepinephrine concentrations in blood. Enlargement of the spleen was also found in the social defeat and "social threat" groups. At the immunological level (Experiment 4), the social defeat group showed lower levels of pro-inflammatory cytokines in the hypothalamus and hippocampus but higher concentration of IL-6 in the striatum compared to the other two groups. At the neurochemical level (Experiment 5), the socially defeated hamsters mainly displayed reductions of dopamine, dopamine metabolites, and 5-HT levels in the striatum and decreased level of 5-HT in the hippocampus. In Experiment 6, an increase in the spine density of hippocampal CA1 pyramidal neurons was specifically observed in the "social threat" group. Collectively, our findings indicate that repeated, intermittent social defeats throughout entire adolescence in hamsters impact their adult responses at multiple levels. Our results also suggest that the "social threat" group may serve as an appropriate control. This study further suggest that the alterations of behavioral responses and neurobiological functions in the body and brain might provide potential markers to measure the negative consequences of chronic social defeats.

A new method for studying social eavesdropping using male golden hamsters.

Social eavesdropping is a special type of social learning and it is defined as the act of extracting information from social interactions between conspecifics. Social eavesdropping has advantages in information gathering and has attracted increasing attention. Emerging studies on social eavesdropping have been reported in several species, but the lack of suitable and manipulable laboratory rodent models remains a challenge to the study of the underlying mechanisms of social eavesdropping. The aim of this study was to take advantage of golden hamsters and their agonistic behaviors to develop a new laboratory method to study social eavesdropping. Male hamsters with or without a defeat experience were used as bystanders and were exposed to either a fighting interaction or a neutral encounter between two male demonstrators in a social learning chamber for a 3-day social learning. The behavioral responses of the bystanders toward observed demonstrators were tested in a U-shaped maze before and after the 3-day social learning. We found that (1) bystanders were attracted to the winning demonstrators in both short-term and long-term tests in experiment 1; (2) bystanders with a brief defeat experience displayed the opposite behavioral pattern and avoided approaching the winning demonstrator in experiment 2. It is evident that these hamsters acquired information about the relative qualities and dominance of the demonstrators and behaved differently toward different conspecifics afterward. Collectively, male hamsters are capable of social eavesdropping and prior experience of defeat has a significant impact on their consequent behaviors. Our newly developed behavioral method offers several advantages and it is useful for the study of social eavesdropping and its underlying mechanisms.