This article has been retracted: please see Elsevier Policy on Article Withdrawal (http://www.elsevier.com/locate/withdrawalpolicy). This article has been retracted at the request of the Editor-in-Chief. Concern has been raised by a reader that research reported in the article duplicates figures and reuses data from prior publications without attribution. After investigation of the concerns raised, the editors found the following reuse of data without attribution: Figure 1B in this article is identical to Ma et al., 2020, FASEB J. 34, 10342–10356, https://doi.org/10.1096/fj.201903157R, Figure 2B. Figure 1D in this article is identical to Ma et al., 2019, Mol. Ther. Nucleic Acids 18, 1049–1062, https://doi.org/10.1016/j.omtn.2019.10.030, Figure 2A. Figure 1F in this article is identical to Ma et al., 2019, Mol. Ther. Nucleic Acids 18, 1049–1062, https://doi.org/10.1016/j.omtn.2019.10.030, Figure 2B. Figure 1A in this article reuses data from Ma et al., 2020, FASEB J. 34, 10342–10356, https://doi.org/10.1096/fj.201903157R, Figure 2E. Figure S1 in this article is identical to Ma et al., 2019, Mol. Ther. Nucleic Acids 18, 1049–1062, https://doi.org/10.1016/j.omtn.2019.10.030, Figure 3 One of the conditions of submission of a paper for publication is that authors declare explicitly that the paper has not been previously published and is not under consideration for publication elsewhere. As such this article represents a misuse of the scientific publishing system. The corresponding authors have agreed to the retraction.

Tubby-like proteins (TULPs) are characterized by a conserved C-terminal domain that binds phosphoinositides. Collectively, mammalian TULP1-4 proteins play essential roles in intracellular transport, cell differentiation, signaling, and motility. Yet, little is known about how the function of these proteins is regulated in cells. Here, we present the protein-protein interaction network of TULP3, a protein that is responsible for the trafficking of G-protein-coupled receptors to cilia and whose aberrant expression is associated with severe developmental disorders and polycystic kidney disease. We identify several protein interaction nodes linked to TULP3 that include enzymes involved in acetylation and ubiquitination. We show that acetylation of two key lysine residues on TULP3 by p300 increases TULP3 protein abundance and that deacetylation of these sites by HDAC1 decreases protein levels. Furthermore, we show that one of these sites is ubiquitinated in the absence of acetylation and that acetylation inversely correlates with ubiquitination of TULP3. This mechanism is evidently conserved across species and is active in zebrafish during development. Finally, we identify this same regulatory module in TULP1, TULP2, and TULP4 and demonstrate that the stability of these proteins is similarly modulated by an acetylation switch. This study unveils a signaling pathway that links nuclear enzymes to ciliary membrane receptors via TULP3, describes a dynamic mechanism for the regulation of all tubby-like proteins, and explores how to exploit it pharmacologically using drugs.

Tubby domain superfamily protein (TUSP) is a distant member of the Tubby-like protein (TULP) family. Although other TULPs play important roles in sensation, metabolism, and development, the molecular functions of TUSP are completely unknown. Here, we explore the function of TUSP in the Drosophila nervous system where it is expressed in all neurons. Tusp mutant flies exhibit a temperature-sensitive paralysis. This paralysis can be rescued by tissue-specific expression of Tusp in the giant fibers and peripherally synapsing interneurons of the giant fiber system, a well-characterized neuronal circuit that mediates rapid escape behavior in flies. Consistent with this paralytic phenotype, we observed a profound reduction in the assembly of the ternary 7S SNARE complex that is required for neurotransmitter release despite seeing no changes in the expression of each individual SNARE complex component. Together, these data suggest TUSP is a novel regulator of SNARE assembly and, therefore, of neurotransmitter release.