From phosphorylation to phenotype - Recent key findings on kinase regulation, downstream signaling and disease surrounding the receptor tyrosine kinase MuSK.

Muscle-specific kinase (MuSK) is the key regulator of neuromuscular junction development. MuSK acts via several distinct pathways and is responsible for pre- and postsynaptic differentiation. MuSK is unique among receptor tyrosine kinases as activation and signaling are particularly tightly regulated. Initiation of kinase activity requires Agrin, a heparan sulphate proteoglycan derived from motor neurons, the low-density lipoprotein receptor-related protein-4 (Lrp4) and the intracellular adaptor protein Dok-7. There is a great knowledge gap between MuSK activation and downstream signaling. Recent studies using omics techniques have addressed this knowledge gap, thereby greatly contributing to a better understanding of MuSK signaling. Impaired MuSK signaling causes severe muscle weakness as described in congenital myasthenic syndromes or myasthenia gravis but the underlying pathophysiology is often unclear. This review focuses on recent advances in deciphering MuSK activation and downstream signaling. We further highlight latest break-throughs in understanding and treatment of MuSK-related disorders and discuss the role of MuSK in non-muscle tissue.

A comparative analysis of the nervous system of cheilostome bryozoans.

BACKGROUND: Bryozoans are sessile aquatic suspension feeders in mainly marine, but also freshwater habitats. Most species belong to the marine and calcified Cheilostomata. Since this taxon remains mostly unstudied regarding its neuroanatomy, the focus of this study is on the characterization and ground pattern reconstruction of the autozooidal nervous system based on six representatives. RESULTS: A common neuronal innervation pattern is present in the investigated species: a cerebral ganglion is located at the base of the lophophore, from where neurite bundles embrace the mouth opening to form a circumoral nerve ring. Four neurite bundles project from the cerebral ganglion to innervate peripheral areas, such as the body wall and parietal muscles via the tentacle sheath. Five neurite bundles comprise the main innervation of the visceral tract. Four neurite bundles innervate each tentacle via the circumoral nerve ring. Mediofrontal tentacle neurite bundles emerge directly from the nerve ring. Two laterofrontal- and one abfrontal tentacle neurite bundles emanate from radial neurite bundles, which originate from the cerebral ganglion and circumoral nerve ring in between two adjacent tentacles. The radial neurite bundles terminate in intertentacular pits and give rise to one abfrontal neurite bundle at the oral side and two abfrontal neurite bundles at the anal side. Similar patterns are described in ctenostome bryozoans. CONCLUSIONS: The present results thus represent the gymnolaemate situation. Innervation of the tentacle sheath and visceral tract by fewer neurite bundles and tentacular innervation by four to six tentacle neurite bundles support cyclostomes as sister taxon to gymnolaemates. Phylactolaemates feature fewer distinct neurite bundles in visceral- and tentacle sheath innervation, which always split in nervous plexus, and their tentacles have six neurite bundles. Thus, this study supports phylactolaemates as sistergroup to myolaemates.