הפקולטה בתקשורת

Degrons are elements within protein substrates that mediate the interaction with specific degradation machineries to control
proteolysis. Recently, a few classes of C-terminal degrons (C-degrons) that are recognized by dedicated cullin-RING ligases
(CRLs) have been identified. Specifically, CRL2 using the related substrate adapters FEM1A/B/C was found to recognize C
degrons ending with arginine (Arg/C-degron). Here, we uncover the molecular mechanism of Arg/C-degron recognition by
solving a subset of structures of FEM1 proteins in complex with Arg/C-degron-bearing substrates. Our structural research,
complemented by binding assays and global protein stability (GPS) analyses, demonstrates that FEM1A/C and FEM1B selectively
target distinct classes of Arg/C-degrons. Overall, our study not only sheds light on the molecular mechanism underlying
Arg/C-degron recognition for precise control of substrate turnover, but also provides valuable information for development of
chemical probes for selectively regulating proteostasis.

Living in a group creates a complex and dynamic environment in which behavior of individuals is influenced by and affects the behavior of others. Although social interaction and group living are fundamental adaptations exhibited by many organisms, little is known about how prior social experience, internal states, and group composition shape behavior in groups. Here, we present an analytical framework for studying the interplay between social experience and group interaction in Drosophila melanogaster. We simplified the complexity of interactions in a group using a series of experiments in which we controlled the social experience and motivational states of individuals to compare behavioral patterns and social networks of groups under different conditions. We show that social enrichment promotes the formation of distinct group structure that is characterized by high network modularity, high inter-individual and inter-group variance, high inter-individual coordination, and stable social clusters. Using environmental and genetic manipulations, we show that visual cues and cVA-sensing neurons are necessary for the expression of social interaction and network structure in groups. Finally, we explored the formation of group behavior and structure in heterogenous groups composed of flies with distinct internal states and documented emergent structures that are beyond the sum of the individuals that constitute it. Our results demonstrate that fruit flies exhibit complex and dynamic social structures that are modulated by the experience and composition of different individuals within the group. This paves the path for using simple model organisms to dissect the neurobiology of behavior in complex social environments.