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Cited by 195Cellular transport and secretionCalcium signaling and nucleotide metabolismLipid metabolism and biosynthesis

Phosphoinositide conversion in endocytosis and the endolysosomal system

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Wallroth, Alexander, Haucke, Volker·2018·Journal of Biological Chemistry
DOI 10.1074/jbc.r117.000629PMC PMC5798284
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Abstract

Phosphoinositides (PIs) are phospholipids that perform crucial cell functions, ranging from cell migration and signaling to membrane trafficking, by serving as signposts of compartmental membrane identity. Although phosphatidylinositol 4,5-bisphosphate, 3-phosphate, and 3,5-bisphosphate are commonly considered as hallmarks of the plasma membrane, endosomes, and lysosomes, these compartments contain other functionally important PIs. Here, we review the roles of PIs in different compartments of the endolysosomal system in mammalian cells and discuss the mechanisms that spatiotemporally control PI conversion in endocytosis and endolysosomal membrane dynamics during endosome maturation and sorting. As defective PI conversion underlies human genetic diseases, including inherited myopathies, neurological disorders, and cancer, PI-converting enzymes represent potential targets for drug-based therapies.

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  • PI(4,5)P2 is dephosphorylated by 5-phosphatases for uncoating to take place; excess PI(4,5)P2 inhibits endocytosis by preventing uncoating and subsequent vesicular fusion.

    “PI(4,5)P2 is dephosphorylated by 5-phosphatases for uncoating to take place [104]. Thus, although PI(4,5)P2 facilitates the mechanism of clathrin vesicle endocytosis, excess PI(4,5)P2 inhibits endocytosis. Persistence of PI(4,5)P2 on vesicular membranes prevents the uncoating of the vesicle and subsequent vesicular fusion with the target membrane [105].”

    From Phosphatidylinositol(4,5)bisphosphate: diverse functions at the plasma membrane (2020) · cites this paper as [104]

    The section on PI(4,5)P2 conversion during coated-pit maturation says that 5-phosphatases hydrolyze PI(4,5)P2 and that loss of these enzymes impairs endocytosis and causes clathrin-coated vesicles to accumulate. It does not explicitly establish that dephosphorylation is required for uncoating, or that persistent PI(4,5)P2 prevents subsequent fusion with a target membrane. The latter statement has a separate citation [105] in the citing text. (LLM, conf=0.82)

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Cited by

Sorted by citations

Authors
Wallroth, A., & Haucke, V.
Affiliations
Leibniz-Forschungsinstitut für Molekulare Pharmakologie (DE)
Corresponding author
Haucke, Volker
ORCID
Venue
Journal of Biological Chemistry
Publisher
Elsevier BV
Published
2018-02
Volume
293
Issue
5
Pages
1526-1535
ISSN
0021-9258 (ISSN-L)
DOI
10.1074/jbc.r117.000629
PMC
PMC5798284
OpenAlex
W2777554180
Cited by
195
References
5
Citations by year
2026: 12 · 2025: 18 · 2024: 29 · 2023: 19 · 2022: 28 · 2021: 32 · 2020: 27 · 2019: 21 · 2018: 9
FWCI
1.82
Type
journal article
Language
en
Open access
Licence
Locations
  • Journal of Biological Chemistry (publishedVersion, cc-by)
  • Europe PMC (PubMed Central) (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
Funders
Deutsche Forschungsgemeinschaft (TRR186, TPA08, SFB740)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular transport and secretion
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Physiology › Calcium signaling and nucleotide metabolism
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Lipid metabolism and biosynthesis
Keywords
phosphoinositides, endocytosis, endolysosomal system, endosome maturation, membrane trafficking, phosphatidylinositol 4,5-bisphosphate, phosphatidylinositol 3-phosphate, phosphatidylinositol 3,5-bisphosphate, lysosomes, inherited myopathies, neurological disorders, cancer, therapeutic target
MeSH terms
Animals, Endocytosis, Humans, Lysosomes, Endosomes, Signal Transduction, Phosphatidylinositol Phosphates, ras Proteins

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