Matches in SemOpenAlex for { <https://semopenalex.org/work/W2024797145> ?p ?o ?g. }
- W2024797145 endingPage "2749" @default.
- W2024797145 startingPage "2734" @default.
- W2024797145 abstract "Phosphatidylinositol 4,5-bisphosphate (PI(4,5)P2) is an essential determinant in clathrin-mediated endocytosis (CME). In mammals three type I phosphatidylinositol-4-phosphate 5-kinase (PIPK) enzymes are expressed, with the Iγ-p90 isoform being highly expressed in the brain where it regulates synaptic vesicle (SV) exo-/endocytosis at nerve terminals. How precisely PI(4,5)P2 metabolism is controlled spatially and temporally is still uncertain, but recent data indicate that direct interactions between type I PIPK and components of the endocytic machinery, in particular the AP-2 adaptor complex, are involved. Here we demonstrated that PIPKIγ-p90 associates with both the μ and β2 subunits of AP-2 via multiple sites. Crystallographic data show that a peptide derived from the splice insert of the human PIPKIγ-p90 tail binds to a cognate recognition site on the sandwich subdomain of the β2 appendage. Partly overlapping aromatic and hydrophobic residues within the same peptide also can engage the C-terminal sorting signal binding domain of AP-2μ, thereby potentially competing with the sorting of conventional YXXØ motif-containing cargo. Biochemical and structure-based mutagenesis analysis revealed that association of the tail domain of PIPKIγ-p90 with AP-2 involves both of these sites. Accordingly the ability of overexpressed PIPKIγ tail to impair endocytosis of SVs in primary neurons largely depends on its association with AP-2β and AP-2μ. Our data also suggest that interactions between AP-2 and the tail domain of PIPKIγ-p90 may serve to regulate complex formation and enzymatic activity. We postulate a model according to which multiple interactions between PIPKIγ-p90 and AP-2 lead to spatiotemporally controlled PI(4,5)P2 synthesis during clathrin-mediated SV endocytosis. Phosphatidylinositol 4,5-bisphosphate (PI(4,5)P2) is an essential determinant in clathrin-mediated endocytosis (CME). In mammals three type I phosphatidylinositol-4-phosphate 5-kinase (PIPK) enzymes are expressed, with the Iγ-p90 isoform being highly expressed in the brain where it regulates synaptic vesicle (SV) exo-/endocytosis at nerve terminals. How precisely PI(4,5)P2 metabolism is controlled spatially and temporally is still uncertain, but recent data indicate that direct interactions between type I PIPK and components of the endocytic machinery, in particular the AP-2 adaptor complex, are involved. Here we demonstrated that PIPKIγ-p90 associates with both the μ and β2 subunits of AP-2 via multiple sites. Crystallographic data show that a peptide derived from the splice insert of the human PIPKIγ-p90 tail binds to a cognate recognition site on the sandwich subdomain of the β2 appendage. Partly overlapping aromatic and hydrophobic residues within the same peptide also can engage the C-terminal sorting signal binding domain of AP-2μ, thereby potentially competing with the sorting of conventional YXXØ motif-containing cargo. Biochemical and structure-based mutagenesis analysis revealed that association of the tail domain of PIPKIγ-p90 with AP-2 involves both of these sites. Accordingly the ability of overexpressed PIPKIγ tail to impair endocytosis of SVs in primary neurons largely depends on its association with AP-2β and AP-2μ. Our data also suggest that interactions between AP-2 and the tail domain of PIPKIγ-p90 may serve to regulate complex formation and enzymatic activity. We postulate a model according to which multiple interactions between PIPKIγ-p90 and AP-2 lead to spatiotemporally controlled PI(4,5)P2 synthesis during clathrin-mediated SV endocytosis." @default.
- W2024797145 created "2016-06-24" @default.
- W2024797145 creator A5008249625 @default.
- W2024797145 creator A5009134392 @default.
- W2024797145 creator A5009884599 @default.
- W2024797145 creator A5010631390 @default.
- W2024797145 creator A5019000351 @default.
- W2024797145 creator A5020274297 @default.
- W2024797145 creator A5033566983 @default.
- W2024797145 creator A5044758922 @default.
- W2024797145 creator A5088746794 @default.
- W2024797145 date "2010-01-01" @default.
- W2024797145 modified "2023-10-16" @default.
- W2024797145 title "Molecular Basis for Association of PIPKIγ-p90 with Clathrin Adaptor AP-2" @default.
- W2024797145 cites W1539796472 @default.
- W2024797145 cites W1965940344 @default.
- W2024797145 cites W1974646226 @default.
- W2024797145 cites W1985685023 @default.
- W2024797145 cites W1985919575 @default.
- W2024797145 cites W1987672004 @default.
- W2024797145 cites W1993054972 @default.
- W2024797145 cites W1996745379 @default.
- W2024797145 cites W2004187559 @default.
- W2024797145 cites W2005458602 @default.
- W2024797145 cites W2006189175 @default.
- W2024797145 cites W2019196882 @default.
- W2024797145 cites W2026134505 @default.
- W2024797145 cites W2026862088 @default.
- W2024797145 cites W2028375489 @default.
- W2024797145 cites W2035503835 @default.
- W2024797145 cites W2036286128 @default.
- W2024797145 cites W2048451267 @default.
- W2024797145 cites W2048973111 @default.
- W2024797145 cites W2056086918 @default.
- W2024797145 cites W2056189730 @default.
- W2024797145 cites W2063458187 @default.
- W2024797145 cites W2078269238 @default.
- W2024797145 cites W2084302112 @default.
- W2024797145 cites W2084671947 @default.
- W2024797145 cites W2089157578 @default.
- W2024797145 cites W2091884933 @default.
- W2024797145 cites W2094882170 @default.
- W2024797145 cites W2104927620 @default.
- W2024797145 cites W2111469080 @default.
- W2024797145 cites W2118447752 @default.
- W2024797145 cites W2119260049 @default.
- W2024797145 cites W2120848575 @default.
- W2024797145 cites W2144420636 @default.
- W2024797145 cites W2148277919 @default.
- W2024797145 cites W2157963288 @default.
- W2024797145 cites W2160658743 @default.
- W2024797145 cites W2168729369 @default.
- W2024797145 cites W2322129974 @default.
- W2024797145 cites W4211068025 @default.
- W2024797145 doi "https://doi.org/10.1074/jbc.m109.074906" @default.
- W2024797145 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/2807329" @default.
- W2024797145 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/19903820" @default.
- W2024797145 hasPublicationYear "2010" @default.
- W2024797145 type Work @default.
- W2024797145 sameAs 2024797145 @default.
- W2024797145 citedByCount "25" @default.
- W2024797145 countsByYear W20247971452012 @default.
- W2024797145 countsByYear W20247971452013 @default.
- W2024797145 countsByYear W20247971452014 @default.
- W2024797145 countsByYear W20247971452015 @default.
- W2024797145 countsByYear W20247971452016 @default.
- W2024797145 countsByYear W20247971452017 @default.
- W2024797145 countsByYear W20247971452018 @default.
- W2024797145 countsByYear W20247971452019 @default.
- W2024797145 countsByYear W20247971452021 @default.
- W2024797145 countsByYear W20247971452023 @default.
- W2024797145 crossrefType "journal-article" @default.
- W2024797145 hasAuthorship W2024797145A5008249625 @default.
- W2024797145 hasAuthorship W2024797145A5009134392 @default.
- W2024797145 hasAuthorship W2024797145A5009884599 @default.
- W2024797145 hasAuthorship W2024797145A5010631390 @default.
- W2024797145 hasAuthorship W2024797145A5019000351 @default.
- W2024797145 hasAuthorship W2024797145A5020274297 @default.
- W2024797145 hasAuthorship W2024797145A5033566983 @default.
- W2024797145 hasAuthorship W2024797145A5044758922 @default.
- W2024797145 hasAuthorship W2024797145A5088746794 @default.
- W2024797145 hasBestOaLocation W20247971452 @default.
- W2024797145 hasConcept C156407911 @default.
- W2024797145 hasConcept C170493617 @default.
- W2024797145 hasConcept C183786373 @default.
- W2024797145 hasConcept C185592680 @default.
- W2024797145 hasConcept C2780976139 @default.
- W2024797145 hasConcept C28005876 @default.
- W2024797145 hasConcept C55493867 @default.
- W2024797145 hasConcept C62478195 @default.
- W2024797145 hasConcept C63162447 @default.
- W2024797145 hasConcept C79747257 @default.
- W2024797145 hasConcept C86803240 @default.
- W2024797145 hasConcept C95444343 @default.
- W2024797145 hasConceptScore W2024797145C156407911 @default.
- W2024797145 hasConceptScore W2024797145C170493617 @default.
- W2024797145 hasConceptScore W2024797145C183786373 @default.
- W2024797145 hasConceptScore W2024797145C185592680 @default.