Disease relevance of ena

• We have used in vitro motility assays of Listeria in platelet and brain extracts to elucidate the function of the focal adhesion proteins of the Ena (Drosophila Enabled)/VASP (vasodilator-stimulated phosphoprotein) family in actin-based motility [1].

High impact information on ena

• Genetic interactions support a model in which Abl functions to antagonize Robo signaling, while Ena is required in part for Robo's repulsive output [2].
• Mena, a relative of VASP and Drosophila Enabled, is implicated in the control of microfilament dynamics [3].
• We also found that pre- but not postsynaptic gain-of-function Sema-1a was able to disrupt the GF-motor neuron synapse and that the phenotype depended on a proline-rich intracellular domain that contains a putative Enabled binding site [4].
• Genetic interactions implicate both Enabled and Trio in LAR signal transduction [5].
• In contrast, CAP-a Drosophila homologue of Adenylyl Cyclase Associated Proteins-functions specifically to limit actin-filament formation catalysed by Ena at apical cell junctions [6].

Biological context of ena

• Conversely, heterozygosity for ena reduces the severity of the CNS phenotype in fra, Netrin and trio,Abl mutants [7].
• Both proteins activate the kinase activity of Abl as assayed by phosphorylation of the Drosophila Enabled (Ena) protein [8].
• We find that Ena localizes to adherens junctions of most epithelial cells, and that it genetically interacts with the adherens junction protein Armadillo (Arm) during morphogenesis [9].
• The Ena protein sequence has multiple poly-(L-proline) residues with similarity to both profilin and src homology 3 binding sites [10].
• Lastly, we show that the zyx102 gene and Drosophila Ena are co-expressed during oogenesis and early embryogenesis, indicating that the two proteins may be able to interact during the development of the Drosophila egg chamber and early embryo [11].

Anatomical context of ena

• Coimmunoprecipitation from Drosophila cytosol confirmed a physical interaction between Khc and Ena [12].
• These data support the hypothesis that Ena provides a regulated link between signal transduction and cytoskeleton assembly in the developing Drosophila embryo [10].
• Furthermore, Ena and profilin were colocalized in spreading cultured cells [10].
• Laminin-mediated cell spreading caused integrin colocalization with intracellular signaling molecules (PAK and Ena) in a Drosophila neuronal cell line [13].

Associations of ena with chemical compounds

• We have identified six tyrosine residues on Ena that are phosphorylated by Abl in vitro and in vivo [14].
• Mutation of these phosphorylation sites to phenylalanine partially impaired the ability of Ena to restore viability to ena mutant animals, indicating that phosphorylation is required for optimal Ena function [14].
• We report that the proline-rich region of Ena is responsible for this interaction as well as for mediating binding to the src homology 3 domain of the Abelson tyrosine kinase [10].
• Drosophila Enabled, previously identified as a suppressor of the abl mutant phenotype and substrate for Drosophila Abl kinase, had markedly increased phosphotyrosine levels in Bcr-Abl expressing Drosophila, indicating that it is a substrate for Bcr-Abl as well [15].

Physical interactions of ena

• Here, we show that Ena can bind directly to the Drosophila homolog of profilin, chickadee [10].
• Molecular and phylogenetic characterization of Zyx102, a Drosophila orthologue of the zyxin family that interacts with Drosophila Enabled [11].

Enzymatic interactions of ena

• We conclude that a critical function of Drosophila Abl is to phosphorylate and negatively regulate ena protein during neural development [16].

Other interactions of ena

• Two prominent genes that arose from these screens were enabled (Ena) and disabled (Dab) [17].
• This subcellular distribution is dependent on an intact Enabled/Vasp homology 1 domain, suggesting that Homer must bind to one or more of its partners for proper localization [18].

References