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Cited by 129Cellular transport and secretionLipid metabolism and biosynthesisProtein Kinase Regulation and GTPase Signaling

Stimulation of phosphatidylinositol kinase type I-mediated phosphatidylinositol (4,5)-bisphosphate synthesis by AP-2μ–cargo complexes

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Krauss, Michael, Kukhtina, Viktoria, Pechstein, Arndt, Haucke, Volker·2006·Proceedings of the National Academy of Sciences
DOI 10.1073/pnas.0510306103PMC PMC1567676
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Abstract

Phosphatidylinositol (4,5)-bisphosphate [PI(4,5)P 2 ] is an important factor for a variety of cellular functions ranging from cell signaling to actin cytoskeletal dynamics and endocytic membrane traffic. Here, we have identified the clathrin adaptor complex AP-2 as a regulator of phosphatidylinositol 4-phosphate 5-kinase (PIPK)-mediated PI(4,5)P 2 synthesis. AP-2 directly interacts with the kinase core domain of type I PIPK isozymes via its μ2-subunit in vitro and in native protein extracts. Endocytic cargo protein binding to μ2 leads to a potent stimulation of PIPK activity. These data thus identify a positive feedback loop consisting of endocytic cargo proteins, AP-2μ, and PIPK type I which may provide a specific pool of PI(4,5)P 2 dedicated to clathrin/AP-2-dependent receptor internalization.

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  • AP2 activates PIP 5-kinase for increased PI(4,5)P2 production, promoting further AP2 recruitment and assembly of endocytic vesicles.

    “A positive feedback loop is also established as AP2 activates PIP 5-kinase for increased PI(4,5)P2 production, promoting further recruitment of AP2 and assembly of endocytic vesicles [100].”

    From Phosphatidylinositol(4,5)bisphosphate: diverse functions at the plasma membrane (2020) · cites this paper as [100]

    The Results report that AP-2μ–cargo complexes activate PI(4,5)P2-synthesizing PIPK, and the Discussion links PI(4,5)P2 to AP-2 membrane association and endocytic coated-pit formation. But the Discussion says this mechanism could provide a positive feedback loop; it does not establish that the loop drives endocytic vesicle assembly as the citing sentence states. (LLM, conf=0.88)

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Cited by

Sorted by citations

Authors
Krauss, M., Kukhtina, V., Pechstein, A., & Haucke, V.
Affiliations
  • Freie Universität Berlin (DE)
  • Yale University (US)
Corresponding author
Haucke, Volker
ORCID
Venue
Proceedings of the National Academy of Sciences
Publisher
National Academy of Sciences
Published
2006-08-08
Volume
103
Issue
32
Pages
11934-11939
ISSN
  • 0027-8424 (ISSN-L)
  • 1091-6490
DOI
10.1073/pnas.0510306103
PMC
PMC1567676
OpenAlex
W2078269238
Cited by
129
References
1
Citations by year
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FWCI
5.52
Type
journal article
Language
en
Open access
Locations
  • Proceedings of the National Academy of Sciences (publishedVersion)
  • Europe PMC (PubMed Central) (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • European Molecular Biology Organization
  • Yale University
  • Michigan State University
  • Deutsche Forschungsgemeinschaft (GRK1123)
  • College of Engineering, Michigan State University
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular transport and secretion
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Lipid metabolism and biosynthesis
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Kinase Regulation and GTPase Signaling
Keywords
phosphatidylinositol 4,5-bisphosphate, phosphatidylinositol 4-phosphate 5-kinase, receptor internalization, positive feedback loop
MeSH terms
Animals, Chlorocebus aethiops, Cytoskeleton, Fibroblasts, HeLa Cells, Humans, Protein Binding, Phosphotransferases (Alcohol Group Acceptor), Phosphatidylinositol 4,5-Diphosphate, COS Cells, Protein Isoforms, Feedback, Physiological, Adaptor Protein Complex 2, Adaptor Protein Complex mu Subunits, Transcription Factor AP-2

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