Abstract
Protein homeostasis serves as an important step in regulating diverse cellular processes underlying the function and development of the nervous system. In particular, the ubiquitination proteasome system (UPS), a universal pathway mediating protein degradation, contributes to the development of numerous synaptic structures, including the Drosophila olfactory-associative learning center mushroom body (MB), thereby affecting associated function. Here, we describe the function of a newly characterized Drosophila F-box protein CG5003, an adaptor for the RING-domain type E3 ligase (SCF complex), in MB development. Lacking CG5003 ubiquitously causes MB γ axon pruning defects and selective CG5003 expression in pan-neurons leads to both γ axon and α/β lobe abnormalities. Interestingly, change in CG5003 expression in MB neurons does not cause any abnormalities in axons, suggesting that CG5003 functions in cells extrinsic to MB to regulate its development. Mass spectrum analysis indicates that silencing CG5003 expression in all neurons affects expression levels of proteins in the cell and structural morphogenesis, transcription regulator activity, and catalytic activity. Our findings reinforce the importance of UPS and identify a new factor in regulating neuronal development as exemplified by the synaptic structure MB.
Highlights
Diverse behavior outputs rely on compartmentalized brain structures that function in a circuitry fashion
By late larval stage (L3, 3rd instar), γ axons bifurcate into dorsal and medial lobes, both are completely pruned by 18 h after puparium formation (18 h APF), re-projected to form the medial γ lobes in adults. α /β neurons begin in the larval stage to develop with axons projecting along a peduncle tract anteriorly, bifurcates into dorsal α and medial β lobes
Our findings identify a new factor in the pathway, an adaptor F-box protein that regulates the development of mushroom body (MB)
Summary
Diverse behavior outputs rely on compartmentalized brain structures that function in a circuitry fashion. By late larval stage (L3, 3rd instar), γ axons bifurcate into dorsal and medial lobes, both are completely pruned by 18 h after puparium formation (18 h APF), re-projected to form the medial γ lobes in adults. Α /β neurons begin in the larval stage to develop with axons projecting along a peduncle tract anteriorly, bifurcates into dorsal α and medial β lobes. CG5003 Regulates Axon Pruning of puparium formation These developmental and remodeling events make MB a great system to analyze intrinsic or extrinsic mechanisms regulating neuronal development. The S phase kinase-associated protein 1 (SKP1)–cullin 1 (CUL1)–Fbox protein (SCF) complex, a better-studied multi-subunit RING-type E3 ligase, provides the substrate specificity via the adaptor F-box protein (Ho et al, 2006, 2008). Substrates targeted for ubiquitination are often phosphorylated and interact with the substrate-binding domain of F-box protein (like WD repeats or leucine-rich repeats LRR)
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