A Novel Mutation in an NPXY Motif of β Integrin Reveals Phenotypes Similar to him-4/hemicentin
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...
| Main Authors: | , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Frontiers Media S.A.
2019-10-01
|
| Series: | Frontiers in Cell and Developmental Biology |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/article/10.3389/fcell.2019.00247/full |
| _version_ | 1819151905710931968 |
|---|---|
| author | Zhongqiang Qiu Peter Sheesley Jeong H. Ahn Eun-Jeong Yu Myeongwoo Lee |
| author_facet | Zhongqiang Qiu Peter Sheesley Jeong H. Ahn Eun-Jeong Yu Myeongwoo Lee |
| author_sort | Zhongqiang Qiu |
| collection | DOAJ |
| description | 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 βpat-3 integrin of Caenorhabditis elegans. 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 βpat-3 integrin causes a phenotype similar to that of Him mutant. Further analyses revealed that males of pat-3(Y804E) and him-4/hemicentin share additional phenotypes such as abnormal gonad and unsuccessful mating. A pat-3 transgenic rescue mutant with a non-polar phenylalanine (F) in NPXY, pat-3(Y792/804F), suppressed the high male number, defective mating, inviable zygote, and the abnormal gonad of him-4 mutants, indicating that Y to F mutation in both NPXY motifs suppressed the him-4 phenotypes. This finding supports the idea that the ECM determines the activation state in integrin NPXY motifs; him-4/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. |
| first_indexed | 2024-12-22T14:40:50Z |
| format | Article |
| id | doaj.art-96b4e2d3aec541bfb091f1a4ff294c68 |
| institution | Directory Open Access Journal |
| issn | 2296-634X |
| language | English |
| last_indexed | 2024-12-22T14:40:50Z |
| publishDate | 2019-10-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Cell and Developmental Biology |
| spelling | doaj.art-96b4e2d3aec541bfb091f1a4ff294c682022-12-21T18:22:33ZengFrontiers Media S.A.Frontiers in Cell and Developmental Biology2296-634X2019-10-01710.3389/fcell.2019.00247481695A Novel Mutation in an NPXY Motif of β Integrin Reveals Phenotypes Similar to him-4/hemicentinZhongqiang QiuPeter SheesleyJeong H. AhnEun-Jeong YuMyeongwoo LeeIntegrin, 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 βpat-3 integrin of Caenorhabditis elegans. 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 βpat-3 integrin causes a phenotype similar to that of Him mutant. Further analyses revealed that males of pat-3(Y804E) and him-4/hemicentin share additional phenotypes such as abnormal gonad and unsuccessful mating. A pat-3 transgenic rescue mutant with a non-polar phenylalanine (F) in NPXY, pat-3(Y792/804F), suppressed the high male number, defective mating, inviable zygote, and the abnormal gonad of him-4 mutants, indicating that Y to F mutation in both NPXY motifs suppressed the him-4 phenotypes. This finding supports the idea that the ECM determines the activation state in integrin NPXY motifs; him-4/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.https://www.frontiersin.org/article/10.3389/fcell.2019.00247/fullpat-3basement membranenegatively chargedglutamic acidgerm cellmale mating |
| spellingShingle | Zhongqiang Qiu Peter Sheesley Jeong H. Ahn Eun-Jeong Yu Myeongwoo Lee A Novel Mutation in an NPXY Motif of β Integrin Reveals Phenotypes Similar to him-4/hemicentin Frontiers in Cell and Developmental Biology pat-3 basement membrane negatively charged glutamic acid germ cell male mating |
| title | A Novel Mutation in an NPXY Motif of β Integrin Reveals Phenotypes Similar to him-4/hemicentin |
| title_full | A Novel Mutation in an NPXY Motif of β Integrin Reveals Phenotypes Similar to him-4/hemicentin |
| title_fullStr | A Novel Mutation in an NPXY Motif of β Integrin Reveals Phenotypes Similar to him-4/hemicentin |
| title_full_unstemmed | A Novel Mutation in an NPXY Motif of β Integrin Reveals Phenotypes Similar to him-4/hemicentin |
| title_short | A Novel Mutation in an NPXY Motif of β Integrin Reveals Phenotypes Similar to him-4/hemicentin |
| title_sort | novel mutation in an npxy motif of β integrin reveals phenotypes similar to him 4 hemicentin |
| topic | pat-3 basement membrane negatively charged glutamic acid germ cell male mating |
| url | https://www.frontiersin.org/article/10.3389/fcell.2019.00247/full |
| work_keys_str_mv | AT zhongqiangqiu anovelmutationinannpxymotifofbintegrinrevealsphenotypessimilartohim4hemicentin AT petersheesley anovelmutationinannpxymotifofbintegrinrevealsphenotypessimilartohim4hemicentin AT jeonghahn anovelmutationinannpxymotifofbintegrinrevealsphenotypessimilartohim4hemicentin AT eunjeongyu anovelmutationinannpxymotifofbintegrinrevealsphenotypessimilartohim4hemicentin AT myeongwoolee anovelmutationinannpxymotifofbintegrinrevealsphenotypessimilartohim4hemicentin AT zhongqiangqiu novelmutationinannpxymotifofbintegrinrevealsphenotypessimilartohim4hemicentin AT petersheesley novelmutationinannpxymotifofbintegrinrevealsphenotypessimilartohim4hemicentin AT jeonghahn novelmutationinannpxymotifofbintegrinrevealsphenotypessimilartohim4hemicentin AT eunjeongyu novelmutationinannpxymotifofbintegrinrevealsphenotypessimilartohim4hemicentin AT myeongwoolee novelmutationinannpxymotifofbintegrinrevealsphenotypessimilartohim4hemicentin |