GO:0034684 integrin alphav-beta5 complex

The integrin alphav-beta5 complex (GO:0034684) is a heterodimeric transmembrane adhesion receptor in the integrin family, formed by non-covalent association of one alphav (ITGAV) subunit and one beta5 (ITGB5) subunit. Integrins are the principal receptors that mediate cell-extracellular matrix and cell-cell interactions, and the alphav-beta5 heterodimer is a well-characterized example whose ligand repertoire and signaling outputs have been defined in several physiological contexts. Because the complex couples extracellular cues to intracellular signaling, it is a focal point for studies of metabolism, tissue crosstalk, and tumor biology. A major advance in understanding this complex came from the identification of irisin as a ligand that acts through the alphav-beta5 integrin receptor in a two-step process requiring extracellular Hsp90alpha. This finding placed the alphav-beta5 complex at the center of exercise-induced myokine signaling and opened the door to mechanistic studies in adipose tissue, muscle, brain, and kidney. In parallel, disintegrin proteins from snake venoms have been shown to functionally affect alphav-beta5-dependent glioma cell invasion, highlighting the complex as a target in neuro-oncology. For researchers, GO:0034684 provides a precise annotation unit for cellular-component studies: it specifies the molecular composition of the receptor, its assembly requirements, and its downstream signaling capacity. Understanding this complex is therefore essential for interpreting experiments that manipulate ITGAV or ITGB5, and for designing CRISPR models that test causality in disease-relevant pathways.

GO:0034684 (integrin alphav-beta5 complex) is a cellular-component ontology term defined as an integrin complex that comprises one alphav subunit and one beta5 subunit. In practical terms, it describes the heterodimeric receptor formed by ITGAV and ITGB5 at the cell surface, which functions as a receptor for extracellular ligands such as irisin and mediates intracellular signaling through pathways including FAK.

The integrin alphav-beta5 complex is important because it translates extracellular signals into intracellular responses that influence energy balance, tissue crosstalk, and tumor cell behavior. Its identification as the irisin receptor established a molecular link between exercise, myokine signaling, and metabolic control, with FAK as a key downstream effector in beige adipocytes. In addition, the complex participates in muscle-brain and muscle-renal communication, where irisin-mediated signaling protects against contrast-induced acute kidney injury by inhibiting cGAS-STING. Finally, functional studies with snake venom disintegrins show that alphav-beta5 integrin modulates glioma cell invasion, underscoring its relevance in cancer biology.

The following genes and proteins are directly or functionally associated with the integrin alphav-beta5 complex (GO:0034684) based on the verified literature.

The integrin alphav-beta5 complex is regulated at multiple levels. Ligand availability, exemplified by irisin, controls receptor activation through a two-step mechanism that requires extracellular Hsp90alpha. Downstream signaling through FAK integrates receptor engagement with cellular growth and metabolic programs in beige fat progenitors. In kidney injury models, irisin-mediated signaling inhibits cGAS-STING, indicating that the complex can modulate innate immune pathways. Disintegrin proteins can also functionally interfere with alphav-beta5 integrin activity, providing an additional layer of regulation relevant to glioma invasion.

The alphav-beta5 integrin complex functions as the receptor for irisin, a myokine that influences energy balance. Downstream FAK signaling controls beige fat progenitor cell growth, linking the complex to metabolic regulation. Dysregulation of this axis may contribute to impaired adipose tissue plasticity and systemic energy imbalance.

Irisin-mediated muscle-renal crosstalk protects against contrast-induced acute kidney injury via cGAS-STING signaling inhibition, a process that depends on integrin receptor signaling. This positions the alphav-beta5 complex as a potential mediator of renoprotective inter-organ communication.

Contortrostatin, a snake venom disintegrin, functionally affects human glioma cell invasion in vitro, implicating alphav-beta5 integrin in tumor cell migration. This suggests the complex may be a target for modulating glioma invasiveness.

Irisin and the muscle-brain axis involve mechanisms with translational potential, and the alphav-beta5 integrin receptor is central to irisin signaling. This raises the possibility that the complex contributes to neuroprotective crosstalk between muscle and brain.

CRISPR knockout of ITGAV or ITGB5 can test whether the alphav-beta5 complex is required for irisin signaling and FAK activation. Point-mutation knock-in can dissect ligand-binding residues and signaling interfaces. These approaches provide causal evidence that complements pharmacological inhibition.

RNA-seq and proteomics can quantify changes in integrin subunits and downstream pathways after perturbation of the complex. Such profiling helps identify FAK-dependent and cGAS-STING-dependent gene programs. It also supports discovery of novel ligands and co-receptors.

Tagged knock-in of ITGAV or ITGB5 enables live-cell imaging of receptor trafficking and surface presentation. Localization studies can reveal how the complex distributes in polarized cells and tissues. These methods are essential for linking receptor position to function.

Glioma invasion assays with disintegrins such as contortrostatin can measure alphav-beta5-dependent migratory behavior. FAK phosphorylation assays report receptor activation status. cGAS-STING reporter assays can quantify downstream innate immune modulation.

Researchers studying integrin alphav-beta5 complex-related genes often need to determine whether a candidate gene is causally involved in receptor assembly, ligand recognition, or downstream signaling. EDITGENE provides CRISPR-based cell models and screening services that enable precise perturbation of ITGAV, ITGB5, and related pathway genes in relevant cellular contexts.

The integrin alphav-beta5 complex (GO:0034684) is a defined heterodimeric receptor with established roles in irisin signaling, FAK-dependent metabolic control, muscle-brain and muscle-renal crosstalk, and glioma invasion. Its precise molecular composition and downstream pathways make it an attractive target for CRISPR-based functional studies. EDITGENE provides the knockout, point-mutation, knock-in, overexpression, and screening tools needed to advance this research.