Deciphering a novel role of the Urm1/Uba4 conjugation machinery for Neuromuscular Junction (NMJ) development in Drosophila melanogaster

• In Drosophila melanogaster, development of the part of the peripheral nervous system that is dedicated to orchestrate locomotion, relies on an intricate interplay between the motor neurons that emanate from the ventral nerve cord, and the body wall musculature that they are destined to innervate. A rather large array of cytoskeletal and signaling proteins are implicated in the formation and growth of the synapses, where motor neurons contact the musculature, specifically at structures known as neuromuscular junctions (NMJs). Master regulators of NMJ development and growth include the WNT, BMP/TGFβ, MAPK, PI3K and JNK signaling pathways. Here we describe a novel role of the ubiquitin-like molecule (UBL) Urm1 (Ubiquitin-related modifier 1) in the regulation of NMJ formation. Specifically, we show that Drosophila Urm1n123 null mutants, as well as flies deficient of the dedicated Urm1 E1 activating enzyme Uba4, Uba4n29, display a significant NMJ overgrowth in third instar larvae, and that Urm1 and Uba4 interact genetically in this process. By utilizing the UAS/GAL4 system, we further provide evidence that Urm1 appears to act in both pre- and post-synaptic tissues, but rescue experiments emphasize a primary role of Urm1 in presynaptic motor neurons. In keeping with the previously established link between loss of Urm1 and excessive activation of JNK signaling, we can conclude that there is a strong genetic interaction between Urm1 and Drosophila JNK pathway components also during NMJ formation. Taken together, we have identified a role of the Urm1/Uba4 conjugation machinery in the regulation of NMJ development and growth, putatively induced by enhanced pre-synaptic activation of the JNK pathway.

Ämnesord

NATURVETENSKAP  -- Biologi -- Biokemi och molekylärbiologi (hsv//swe)

NATURAL SCIENCES  -- Biological Sciences -- Biochemistry and Molecular Biology (hsv//eng)

MEDICIN OCH HÄLSOVETENSKAP  -- Klinisk medicin -- Neurologi (hsv//swe)

MEDICAL AND HEALTH SCIENCES  -- Clinical Medicine -- Neurology (hsv//eng)

Nyckelord

molekylärbiologi

Molecular Biology

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