Tks5 Regulates Synaptic Podosome Formation and Stabilization of the Postsynaptic Machinery at the Neuromuscular Junction

Currently, the etiology of many neuromuscular disorders remains unknown. Many of them are characterized by aberrations in the maturation of the neuromuscular junction (NMJ) postsynaptic machinery. Unfortunately, the molecular factors involved in this process are still largely unknown, which poses a great challenge for identifying potential therapeutic targets. Here, we identified Tks5 as a novel interactor of αdystrobrevin-1, which is a crucial component of the NMJ postsynaptic machinery. Tks5 has been previously shown in cancer cells to be an important regulator of actin-rich structures known as invadosomes. However, a role of this scaffold protein at a synapse has never been studied. We show that Tks5 is crucial for remodeling of the NMJ postsynaptic machinery by regulating the organization of structures similar to the invadosomes, known as synaptic podosomes. Additionally, it is involved in the maintenance of the integrity of acetylcholine receptor (AChR) clusters and regulation of their turnover. Lastly, our data indicate that these Tks5 functions may be mediated by its involvement in recruitment of actin filaments to the postsynaptic machinery. Collectively, we show for the first time that the Tks5 protein is involved in regulation of the postsynaptic machinery.     

Graphic modeling in Distributed Autonomous and Asynchronous Automata (DA3)

Automated verification of distributed systems becomes very important in distributed computing. The graphical insight into the system in the early and late stages of the project is essential. In the design phase, the visual input helps to articulate the collaborative distributed components clearly. The formal verification gives evidence of correctness or malfunction, but in the latter case, graphical simulation of counterexample helps for better understanding design errors. For these purposes, we invented Distributed Autonomous and Asynchronous Automata (DA³), which have the same semantics as the formal verification base—Integrated Model of Distributed Systems (IMDS). The IMDS model reflects the natural characteristics of distributed systems: unicasting, locality, autonomy, and asynchrony. Distributed automata have all of these features because they share the same semantics as IMDS. In formalism, the unified system definition has two views: the server view of the cooperating distributed nodes and the agent view of the migrating agents performing distributed computations. The automata have two formally equivalent forms that reflect two views: Server DA³ for observing servers exchanging messages, and Agent DA³ for tracking agents, which visit individual servers in their progress of distributed calculations. We present the DA³ formulation based on the IMDS formalism and their application to design and verify distributed systems in the Dedan environment. DA³ formalism is compared with other concepts of distributed automata known from the literature.