Hunting ecology predicts eye arrangements in the modular visual system of spiders

  Hunting ecology predicts eye arrangements in the modular visual system of spiders Summary Vision is one of the most important senses used by animals and contributes to fundamental behaviors, including foraging, navigation, and mate detection and selection. 1 Although much is known about how eye position and orientation correlate to ecology in the context of binocularity, 2 animals with multipartite visual systems (more than two eyes) remain comparatively neglected. Spiders are highly successful predators that occupy a range of ecological niches and usually possess eight eyes. Here, we use three-dimensional geometric morphometrics and evolutionary modeling to test whether eye positions, orientations, and interocular angles correlate with hunting strategies in 52 species across the spider phylogeny. We demonstrate that eye configurations diversified from an ancestral medial cluster, as seen in modern trapdoor spiders, to a halo-like configuration in orb-weavers, and to the fronta...

GLP-1 receptor agonist properties of a chimeric peptide derived by hybridization of Latrodectus αLatrotoxin and Heloderma Exendin-4

 


GLP-1 receptor agonist properties of a chimeric peptide derived by hybridization of Latrodectus αLatrotoxin and Heloderma Exendin-4

Abstract

Chimeric peptides comprised of amino acid sequence motifs found within hormones, neuropeptides, and insect or lizard toxins are now under investigation for their potential use in therapeutics. Here, we report the discovery of one such peptide designated as Black Widow Spider-Exendin-4 (BW-Ex-4). It consists of a putative G protein-coupled receptor (GPCR) binding domain present within αLatrotoxin (αLTX) isolated from Latrodectus, and fused to N- and C- terminal motifs found within the glucagon-like peptide-1 receptor (GLP-1R) agonist Exendin-4 isolated from Heloderma. FRET reporter assays that monitor cAMP production establish BW-Ex-4 to be a specific GLP-1R agonist without any stimulatory action at glucose-dependent insulinotropic peptide (GIP), glucagon, or corticotropin releasing hormone (CRH) receptors. Structural modeling studies of the predicted BW-Ex-4 binding sites at GPCRs of Family B provide new insights concerning the molecular basis for chimeric peptide stimulatory actions at the GLP-1R. We also report that BW-Ex-4 acts in obese hyperglycemic Leprdb/db mice to suppress appetite, lower body weight, improve glucoregulation, and to reduce circulating levels of pro-inflammatory cytokines. Collectively, these findings establish combinatorial chimeric peptide chemistry in which αLTX serves as a molecular scaffold for the design of hybrid peptides with novel GPCR stimulating properties.
Chepurny, O. G., Liles, A. N., Cham, N., Matsoukas, M., Liapakis, G., Meng, Q., Cooney, R. N., Doyle, R. P., & Holz, G. G. (2025). GLP-1 receptor agonist properties of a chimeric peptide derived by hybridization of Latrodectus αLatrotoxin and Heloderma Exendin-4. General and Comparative Endocrinology, 114745. https://doi.org/10.1016/j.ygcen.2025.114745