Centre for Research on Biomolecular Interactions presents Prof. Vlad Panin, Department of Biochemistry and Biophysics, Texas A&M University, College station, USA

Talk Title: "Sense of sensibility: Function of protein glycosylation in sensory neurons unraveled by Drosophila model"

Abstract: Protein O-mannosylation (POM) is a special type of protein glycosylation that is highly conserved in evolution, with orthologues of POM-generating enzymes being present in animal organisms from Drosophila to humans. The last step of POM biosynthesis is mediated by several glycosyltransferase enzymes that attach O-linked mannose to serine and threonine residues of secretory pathway proteins. These enzymes show distinct specificities towards protein substrates. Protein O-mannosyltransferases 1 and 2 (POMT1/2) are known to modify Dystroglycan (Dg), which is essential for muscle function. POMT mutations result in severe congenital muscular dystrophies and also affect neural development. However, the function of POM in the nervous system is poorly understood. With remarkable conservation of POMTs, Drosophila offers powerful tools to investigate POM in neural development. Our experiments revealed that Drosophila POMTs regulate sensory feedback required for patterning of peristaltic muscle contractions that control body posture. In POMT mutant embryos, connectivity of sensory neurons inside the CNS is abnormal. Mutant sensory axons have defects in branching and crossing midline of the ventral ganglion. Normal wiring of axon termini can be restored in POMT mutants by transgenic expression of POMTs in sensory neurons, which suggests that POMTs have sensory neuron-specific functions. Genetic analyses indicated that POM targets besides Dg could regulate wiring of sensory axons. Involvement of POMTs in control of coordinated muscle contractions and proper connectivity of sensory axon termini uncovers novel POM functions that are expected to be conserved in humans and can shed light on neurological pathomechanisms of muscular dystrophies.

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