Dataset Information

The first quarter of the C-terminal domain of Abelson regulates the WAVE regulatory complex and Enabled in axon guidance.

ABSTRACT: BACKGROUND:Abelson tyrosine kinase (Abl) plays a key role in axon guidance in linking guidance receptors to actin dynamics. The long C-terminal domain (CTD) of Drosophila Abl is important for this role, and previous work identified the 'first quarter' (1Q) of the CTD as essential. Here, we link the physical interactions of 1Q binding partners to Abl's function in axon guidance. METHODS:Protein binding partners of 1Q were identified by GST pulldown and mass spectrometry, and validated using axon guidance assays in the embryonic nerve cord and motoneurons. The role of 1Q was assessed genetically, utilizing a battery of Abl transgenes in combination with mutation or overexpression of the genes of pulled down proteins, and their partners in actin dynamics. The set of Abl transgenes had the following regions deleted: all of 1Q, each half of 1Q ('eighths', 1E and 2E) or a PxxP motif in 2E, which may bind SH3 domains. RESULTS:GST pulldown identified Hem and Sra-1 as binding partners of 1Q, and our genetic analyses show that both proteins function with Abl in axon guidance, with Sra-1 likely interacting with 1Q. As Hem and Sra-1 are part of the actin-polymerizing WAVE regulatory complex (WRC), we extended our analyses to Abi and Trio, which interact with Abl and WRC members. Overall, the 1Q region (and especially 2E and its PxxP motif) are important for Abl's ability to work with WRC in axon guidance. These areas are also important for Abl's ability to function with the actin regulator Enabled. In comparison, 1E contributes to Abl function with the WRC at the midline, but less so with Enabled. CONCLUSIONS:The 1Q region, and especially the 2E region with its PxxP motif, links Abl with the WRC, its regulators Trio and Abi, and the actin regulator Ena. Removing 1E has specific effects suggesting it may help modulate Abl's interaction with the WRC or Ena. Thus, the 1Q region of Abl plays a key role in regulating actin dynamics during axon guidance.

SUBMITTER: Cheong HSJ

PROVIDER: S-EPMC7196227 | biostudies-literature | 2020 May

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

The first quarter of the C-terminal domain of Abelson regulates the WAVE regulatory complex and Enabled in axon guidance.

Cheong Han Sian Joshua HSJ Nona Mark M Guerra Samantha Barbara SB VanBerkum Mark Francis MF

Neural development 20200502 1

<h4>Background</h4>Abelson tyrosine kinase (Abl) plays a key role in axon guidance in linking guidance receptors to actin dynamics. The long C-terminal domain (CTD) of Drosophila Abl is important for this role, and previous work identified the 'first quarter' (1Q) of the CTD as essential. Here, we link the physical interactions of 1Q binding partners to Abl's function in axon guidance.<h4>Methods</h4>Protein binding partners of 1Q were identified by GST pulldown and mass spectrometry, and valida ...[more]

PMID: 32359359

Similar Datasets

Project description:During the development of the Drosophila central nervous system the process of midline crossing is orchestrated by a number of guidance receptors and ligands. Many key axon guidance molecules have been identified in both invertebrates and vertebrates, but the transcriptional regulation of growth cone guidance remains largely unknown. One open question is whether transcriptional regulation plays a role in midline crossing, or if local translation can account for the necessary fine tuning of protein levels. To investigate this issue, we conducted a genome wide analysis of transcription in Drosophila embryos using wild type and a number of well-characterized Drosophila guidance mutants and transgenics. We also analyzed a publicly available microarray time course of Drosophila embryonic development with an axon guidance focus. Using hopach, a novel clustering method which is well suited to microarray data analysis, we identified groups of genes with similar expression patterns across guidance mutants and transgenics. We then systematically characterized the resulting clusters with respect to their relevance to axon guidance using two complementary controlled vocabularies: the Gene Ontology (GO) and anatomical annotations of the Atlas of Pattern of Gene Expression (APoGE) in situ hybridization database. The analysis indicates that regulation of gene expression does play a role in the process of axon guidance in Drosophila. We also find a strong link between axon guidance and hemocyte migration, a result that agrees with mounting evidence that axon guidance molecules are co-opted in vertebrate vascularization. Cell cyclin activity in the context of axon guidance is also suggested from our array data. RNA and protein patterns of cell cyclin in axon guidance mutants and transgenics support this possible link. This study provides important insights into the regulation of axon guidance in vivo and suggests that transcription does play a role in control of axon guidance. Keywords: Mutant Analysis

Dataset Information

The first quarter of the C-terminal domain of Abelson regulates the WAVE regulatory complex and Enabled in axon guidance.

Publications

The first quarter of the C-terminal domain of Abelson regulates the WAVE regulatory complex and Enabled in axon guidance.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets