Inverse regulation of two classic Hippo pathway target genes in Drosophila by the dimerization hub protein Ctp

Barron, Daniel A.; Moberg, Kenneth H.

doi:10.1038/srep22726

Cited by 2 publications

(1 citation statement)

References 62 publications

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“…In addition, a study of the protein interaction network of the mammalian Hippo pathway also revealed interaction between AMOT proteins and LC8 [ 66 ], confirmed by additional large-scale studies [ 67 , 68 ]. A recent work established a connection between LC8 and the Hippo pathway in Drosophila [ 69 ]. In the present work, the LC8 binding sites were experimentally verified both in WWC and the AMOT protein families and were shown to be evolutionarily conserved.…”

Section: Discussionmentioning

confidence: 99%

Novel linear motif filtering protocol reveals the role of the LC8 dynein light chain in the Hippo pathway

et al. 2017

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Protein-protein interactions (PPIs) formed between short linear motifs and globular domains play important roles in many regulatory and signaling processes but are highly underrepresented in current protein-protein interaction databases. These types of interactions are usually characterized by a specific binding motif that captures the key amino acids shared among the interaction partners. However, the computational proteome-level identification of interaction partners based on the known motif is hindered by the huge number of randomly occurring matches from which biologically relevant motif hits need to be extracted. In this work, we established a novel bioinformatic filtering protocol to efficiently explore interaction network of a hub protein. We introduced a novel measure that enabled the optimization of the elements and parameter settings of the pipeline which was built from multiple sequence-based prediction methods. In addition, data collected from PPI databases and evolutionary analyses were also incorporated to further increase the biological relevance of the identified motif hits. The approach was applied to the dynein light chain LC8, a ubiquitous eukaryotic hub protein that has been suggested to be involved in motor-related functions as well as promoting the dimerization of various proteins by recognizing linear motifs in its partners. From the list of putative binding motifs collected by our protocol, several novel peptides were experimentally verified to bind LC8. Altogether 71 potential new motif instances were identified. The expanded list of LC8 binding partners revealed the evolutionary plasticity of binding partners despite the highly conserved binding interface. In addition, it also highlighted a novel, conserved function of LC8 in the upstream regulation of the Hippo signaling pathway. Beyond the LC8 system, our work also provides general guidelines that can be applied to explore the interaction network of other linear motif binding proteins or protein domains.

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Section: Discussionmentioning

confidence: 99%

Novel linear motif filtering protocol reveals the role of the LC8 dynein light chain in the Hippo pathway

et al. 2017

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Control of nerve cord formation by Engrailed and Gooseberry-Neuro: A multi-step, coordinated process

Bonneaud

Layalle

Colomb

et al. 2017

Developmental Biology

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One way to better understand the molecular mechanisms involved in the construction of a nervous system is to identify the downstream effectors of major regulatory proteins. We previously showed that Engrailed (EN) and Gooseberry-Neuro (GsbN) transcription factors act in partnership to drive the formation of posterior commissures in the central nervous system of Drosophila. In this report, we identified genes regulated by both EN and GsbN through chromatin immunoprecipitation ("ChIP on chip") and transcriptome experiments, combined to a genetic screen relied to the gene dose titration method. The genomic-scale approaches allowed us to define 175 potential targets of EN-GsbN regulation. We chose a subset of these genes to examine ventral nerve cord (VNC) defects and found that half of the mutated targets show clear VNC phenotypes when doubly heterozygous with en or gsbn mutations, or when homozygous. This strategy revealed new groups of genes never described for their implication in the construction of the nerve cord. Their identification suggests that, to construct the nerve cord, EN-GsbN may act at three levels, in: (i) sequential control of the attractive-repulsive signaling that ensures contralateral projection of the commissural axons, (ii) temporal control of the translation of some mRNAs, (iii) regulation of the capability of glial cells to act as commissural guideposts for developing axons. These results illustrate how an early, coordinated transcriptional control may orchestrate the various mechanisms involved in the formation of stereotyped neuronal networks. They also validate the overall strategy to identify genes that play crucial role in axonal pathfinding.

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Inverse regulation of two classic Hippo pathway target genes in Drosophila by the dimerization hub protein Ctp

Cited by 2 publications

References 62 publications

Novel linear motif filtering protocol reveals the role of the LC8 dynein light chain in the Hippo pathway

Novel linear motif filtering protocol reveals the role of the LC8 dynein light chain in the Hippo pathway

Control of nerve cord formation by Engrailed and Gooseberry-Neuro: A multi-step, coordinated process

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