A Novel Mutation in an NPXY Motif of β Integrin Reveals Phenotypes Similar to .

Integrin, an αβ heterodimeric cell surface receptor for the extracellular matrix (ECM), carries two tyrosine phosphorylation motifs in the cytoplasmic tail of the β subunit. NPXY (Asn-Pro-x-Tyr) is a conserved tyrosine phosphorylation motif that binds to the phospho-tyrosine binding (PTB) domain. We generated a tyrosine to glutamic acid (E) mutation to modify tyrosine (Y) into a negatively charged amino NPXY in the β integrin of . The transgenic rescue animal displayed defects in gonad migration and tail morphology. Also, the mutant animals produced a high number of males, suggesting that the Y to E mutation in β integrin causes a phenotype similar to that of Him mutant. Further analyses revealed that males of and hemicentin share additional phenotypes such as abnormal gonad and unsuccessful mating. A transgenic rescue mutant with a non-polar phenylalanine (F) in NPXY, , suppressed the high male number, defective mating, inviable zygote, and the abnormal gonad of mutants, indicating that Y to F mutation in both NPXY motifs suppressed the phenotypes. This finding supports the idea that the ECM determines the activation state in integrin NPXY motifs; hemicentin may directly or indirectly interact with integrins and maintain the NPXY non-charged. Our findings provide new insight into a suppressive role of an ECM molecule in integrin NPXY phosphorylation.