The Alk receptor tyrosine kinase regulates Sparkly, a novel activity regulating neuropeptide precursor in the Drosophila central nervous system.

Numerous roles for the Alk receptor tyrosine kinase have been described in Drosophila, including functions in the central nervous system (CNS), however the molecular details are poorly understood. To gain mechanistic insight, we employed Targeted DamID (TaDa) transcriptional profiling to identify targets of Alk signaling in the larval CNS. TaDa was employed in larval CNS tissues, while genetically manipulating Alk signaling output. The resulting TaDa data were analyzed together with larval CNS scRNA-seq datasets performed under similar conditions, identifying a role for Alk in the transcriptional regulation of neuroendocrine gene expression. Further integration with bulk and scRNA-seq datasets from larval brains in which Alk signaling was manipulated identified a previously uncharacterized Drosophila neuropeptide precursor encoded by CG4577 as an Alk signaling transcriptional target. CG4577, which we named Sparkly (Spar), is expressed in a subset of Alk-positive neuroendocrine cells in the developing larval CNS, including circadian clock neurons. In agreement with our TaDa analysis, overexpression of the Drosophila Alk ligand Jeb resulted in increased levels of Spar protein in the larval CNS. We show that Spar protein is expressed in circadian (clock) neurons, and flies lacking Spar exhibit defects in sleep and circadian activity control. In summary, we report a novel activity regulating neuropeptide precursor gene that is regulated by Alk signaling in the Drosophila CNS.

Bioinformatics for Renal and Urinary Proteomics: Call for Aggrandization.

The clinical sampling of urine is noninvasive and unrestricted, whereby huge volumes can be easily obtained. This makes urine a valuable resource for the diagnoses of diseases. Urinary and renal proteomics have resulted in considerable progress in kidney-based disease diagnosis through biomarker discovery and treatment. This review summarizes the bioinformatics tools available for this area of proteomics and the milestones reached using these tools in clinical research. The scant research publications and the even more limited bioinformatic tool options available for urinary and renal proteomics are highlighted in this review. The need for more attention and input from bioinformaticians is highlighted, so that progressive achievements and releases can be made. With just a handful of existing tools for renal and urinary proteomic research available, this review identifies a gap worth targeting by protein chemists and bioinformaticians. The probable causes for the lack of enthusiasm in this area are also speculated upon in this review. This is the first review that consolidates the bioinformatics applications specifically for renal and urinary proteomics.