Integrins are heterodimeric transmembrane receptors that mediate bidirectional interactions between the intracellular cytoskeletal array and the extracellularmatrix.These interactions are critical in tissue developmen...Integrins are heterodimeric transmembrane receptors that mediate bidirectional interactions between the intracellular cytoskeletal array and the extracellularmatrix.These interactions are critical in tissue development and function by regulating gene expression and sustaining tissue architecture.In humans,the integrin family is composed of 18 alpha(α)and 8 beta(β)subunits,constituting 24 distinctαβcombinations.Based on their structure and ligandbinding properties,only a subset of integrins,8 out of 24,recognizes the arginine-glycine-aspartate(RGD)tripeptide motif in the native ligand.One of the major RGD binding integrins is integrin alpha 8 beta 1(α8β1),a central Ras homolog gene familymemberA(RHOA)-dependentmodulator highly expressed in cells with contractile function.This review focuses on the recent advances regardingα8β1 function during organ development,with a particular interest in kidney and inner ear development.We alsodiscussα8β1’s role ininjury anddisease and its importance formesenchymal to epithelial transition during cancer development.Finally,we highlightα8β1’s importance for hearing function and its future use as a potential diagnostic and therapeutic tool for disease elimination.展开更多
基金supported by NIH-NIDCD,5R01DC21070-0,and Creighton University’s Start-up funds to MZMs.Iman Ezzat was supported by the Department of Biomedical Sciences at Creighton University and the Bellucci Foundation pre-doctoral award.
文摘Integrins are heterodimeric transmembrane receptors that mediate bidirectional interactions between the intracellular cytoskeletal array and the extracellularmatrix.These interactions are critical in tissue development and function by regulating gene expression and sustaining tissue architecture.In humans,the integrin family is composed of 18 alpha(α)and 8 beta(β)subunits,constituting 24 distinctαβcombinations.Based on their structure and ligandbinding properties,only a subset of integrins,8 out of 24,recognizes the arginine-glycine-aspartate(RGD)tripeptide motif in the native ligand.One of the major RGD binding integrins is integrin alpha 8 beta 1(α8β1),a central Ras homolog gene familymemberA(RHOA)-dependentmodulator highly expressed in cells with contractile function.This review focuses on the recent advances regardingα8β1 function during organ development,with a particular interest in kidney and inner ear development.We alsodiscussα8β1’s role ininjury anddisease and its importance formesenchymal to epithelial transition during cancer development.Finally,we highlightα8β1’s importance for hearing function and its future use as a potential diagnostic and therapeutic tool for disease elimination.