1000 Titel
  • Molecular Basis for Association of PIPKIγ-p90 with Clathrin Adaptor AP-2
1000 Autor/in
  1. Kahlfeldt, Nina |
  2. Vahedi-Faridi, Ardeschir |
  3. Koo, Seong Joo |
  4. Schäfer, Johannes G. |
  5. Krainer, Georg |
  6. Keller, Sandro |
  7. Saenger, Wolfram |
  8. Krauss, Michael |
  9. Haucke, Volker |
1000 Erscheinungsjahr 2009
1000 LeibnizOpen
1000 Publikationstyp
  1. Artikel |
1000 Online veröffentlicht
  • 2009-11-10
1000 Erschienen in
1000 Quellenangabe
  • 285: 2734-2749
1000 FRL-Sammlung
1000 Verlagsversion
  • https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2807329/ |
  • http://doi.org/10.1074/jbc.M109.074906 |
1000 Ergänzendes Material
  • http://www.jbc.org/content/285/4/2734/suppl/DC1 |
1000 Publikationsstatus
1000 Begutachtungsstatus
1000 Sprache der Publikation
1000 Abstract/Summary
  • 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.
1000 Sacherschließung
lokal Phosphatidylinositol Kinase
lokal Cell/Exocytosis
lokal Cell/Endocytosis
lokal Membrane/Trafficking
lokal Synaptic Vesicle Recycling
lokal Clathrin
1000 Fächerklassifikation (DDC)
1000 Liste der Beteiligten
  1. https://frl.publisso.de/adhoc/creator/S2FobGZlbGR0LCBOaW5h|https://frl.publisso.de/adhoc/creator/VmFoZWRpLUZhcmlkaSwgQXJkZXNjaGly|https://frl.publisso.de/adhoc/creator/S29vLCBTZW9uZyBKb28=|https://frl.publisso.de/adhoc/creator/U2Now6RmZXIsIEpvaGFubmVzIEcu|https://frl.publisso.de/adhoc/creator/S3JhaW5lciwgR2Vvcmc=|https://frl.publisso.de/adhoc/creator/S2VsbGVyLCBTYW5kcm8=|https://frl.publisso.de/adhoc/creator/U2FlbmdlciwgV29sZnJhbQ==|https://frl.publisso.de/adhoc/creator/S3JhdXNzLCBNaWNoYWVs|http://orcid.org/0000-0003-3119-6993
1000 Label
1000 Förderer
  1. German Research Foundation (DFG) |
1000 Fördernummer
  1. HA2686/2-1; HA2686/2-2; FG 806; SFB 449:TP A11; SFB 449:TP Z3; Exc 257-Neurocure
1000 Förderprogramm
  1. -
1000 Förderung
  1. 1000 joinedFunding-child
    1000 Förderer German Research Foundation (DFG) |
    1000 Förderprogramm -
    1000 Fördernummer HA2686/2-1; HA2686/2-2; FG 806; SFB 449:TP A11; SFB 449:TP Z3; Exc 257-Neurocure
1000 Objektart article
1000 Beschrieben durch
1000 @id frl:6403021.rdf
1000 Erstellt am 2017-06-13T11:36:06.964+0200
1000 Erstellt von 25
1000 beschreibt frl:6403021
1000 Bearbeitet von 288
1000 Zuletzt bearbeitet Wed Mar 31 07:25:59 CEST 2021
1000 Objekt bearb. Wed Mar 31 07:25:59 CEST 2021
1000 Vgl. frl:6403021
1000 Oai Id
  1. oai:frl.publisso.de:frl:6403021 |
1000 Sichtbarkeit Metadaten public
1000 Sichtbarkeit Daten public
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