High impact information on Eps8

• Moreover, in Eps8 null mice, NMDA receptor currents and their sensitivity to inhibition by ethanol are abnormal [1].
• In addition, Eps8 null neurons are resistant to the actin-remodeling activities of NMDA and ethanol [1].
• Here we report that mice lacking Eps8, a regulator of actin dynamics, are resistant to some acute intoxicating effects of ethanol and show increased ethanol consumption [1].
• One established function of the Eps8-Abi1 complex is to participate in the activation of the small GTPase Rac, suggesting a multifaceted role for this complex in actin dynamics, possibly through the participation in alternative larger complexes [2].
• Eps8-family proteins do not show any similarity to gelsolin-like proteins [2].

Biological context of Eps8

• The Eps8 family of proteins is implicated in the regulation of actin cytoskeleton remodeling during cell migration, yet the precise mechanism by which Eps8 regulates actin organization and remodeling remains elusive [3].
• Hence, the SH3 domain of Eps8 may represent a dimerization motif [4].
• Thus, depending on its engagement in different complexes, Eps8 participates to EGFR signaling through Rac and endocytosis through Rab5 [5].
• Screening of the Expressed Sequence Tags database allowed the identification of three Eps8-related genes, whose SH3s also display unusual binding preferences and constitute a phylogenetically distinct subfamily within the SH3 family [6].
• Our previous studies indicated that both tyrosyl phosphorylation and protein expression of Eps8 were elevated in v-Src transformed cells [7].

Anatomical context of Eps8

• Eps8 controls actin-based motility by capping the barbed ends of actin filaments [2].
• The morphology of actin structures induced by Eps8 was modulated by interactions with Abi1, which stimulated formation of actin cables in cultured cells and star-like structures in Xenopus [3].
• We also found that Eps8 recruits Dishevelled to the plasma membrane and actin filaments suggesting that Eps8 might participate in non-canonical Wnt/Polarity signaling [3].
• Furthermore, both Eps8 and CD44 mRNA levels were reduced greatly in the brain tissues of the cerebrum isolated from the PrP(-)(/-) mice [8].
• In cycling fibroblasts immunolabeling with antibodies to Eps8 reveals a punctate pattern within the perinuclear region and staining of motile peripheral cell extensions and cell-cell contact regions [9].

Associations of Eps8 with chemical compounds

• Notably, removal of TSA from the medium restored not only the expression of Eps8, but also cellular growth [10].
• We report that the SH3 domain of Eps8, a substrate of receptor and non-receptor tyrosine kinases, displays a novel and unique binding preference [6].
• Extraction with Triton X-100 preserves the association of Eps8 to podosomes and leaves the majority of the v-Src tyrosine-phosphorylated Eps8 in the detergent-resistant fraction [9].

Other interactions of Eps8

• Conversely, full-length Eps8 is auto-inhibited in vitro, and interaction with the Abi1 protein relieves this inhibition [2].
• Moreover, fractionation studies reveal that a portion of the Eps8 molecules present in the cell periphery, unlike cortactin and the receptor, is resistant to mild extraction with detergent [9].

Analytical, diagnostic and therapeutic context of Eps8

• In addition, co-immunoprecipitation experiments show that intact Eps8 is multimeric in vivo [4].

References