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Cited by 24Cellular transport and secretionLipid metabolism and biosynthesisLipid Membrane Structure and Behavior

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A palmitoylation code controls PI4KIIIα complex formation and PI(4,5)P2 homeostasis at the plasma membrane

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Batrouni, Alex G., Bag, Nirmalya, Phan, Henry T., Baird, Barbara A., Baskin, Jeremy M.·2022·Journal of Cell Science
DOI 10.1242/jcs.259365PMC PMC8592054

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Abstract

Phosphatidylinositol 4-kinase IIIα (PI4KIIIα) is the major enzyme responsible for generating phosphatidylinositol (4)-phosphate [PI(4)P] at the plasma membrane. This lipid kinase forms two multicomponent complexes, both including a palmitoylated anchor, EFR3. Whereas both PI4KIIIα complexes support production of PI(4)P, the distinct functions of each complex and mechanisms underlying the interplay between them remain unknown. Here, we present roles for differential palmitoylation patterns within a tri-cysteine motif in EFR3B (Cys5, Cys7 and Cys8) in controlling the distribution of PI4KIIIα between these two complexes at the plasma membrane and corresponding functions in phosphoinositide homeostasis. Spacing of palmitoyl groups within three doubly palmitoylated EFR3B ‘lipoforms’ affects both interactions between EFR3B and TMEM150A, a transmembrane protein governing formation of a PI4KIIIα complex functioning in rapid phosphatidylinositol (4,5)-bisphosphate [PI(4,5)P2] resynthesis following phospholipase C signaling, and EFR3B partitioning within liquid-ordered and -disordered regions of the plasma membrane. This work identifies a palmitoylation code involved in controlling protein–protein and protein–lipid interactions that affect a plasma membrane-resident lipid biosynthetic pathway.

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Metadata

Authors
Batrouni, A. G., Bag, N., Phan, H. T., Baird, B. A., & Baskin, J. M.
Affiliations
Cornell University (US)
Corresponding author
  • Bag, Nirmalya
  • Baskin, Jeremy M.
ORCID
Venue
Journal of Cell Science
Publisher
The Company of Biologists
Published
2021-10-22
Volume
135
Issue
5
ISSN
  • 0021-9533 (ISSN-L)
  • 1477-9137
DOI
10.1242/jcs.259365
PMC
PMC8592054
OpenAlex
W3202222668
Cited by
24
References
1
Citations by year
2026: 7 · 2025: 7 · 2024: 3 · 2023: 4 · 2022: 3
FWCI
1.31
Type
journal article
Language
en
Open access
Licence
www.biologists.com/user-licence-1-1/ (vor)
Locations
  • Journal of Cell Science (publishedVersion)
  • bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by-nc-nd)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • National Institutes of Health (R00GM110121, R01GM131101, R01GM117552)
  • Alfred P. Sloan Foundation
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 › Lipid Membrane Structure and Behavior
Keywords
PI4KIIIα, palmitoylation, phosphatidylinositol 4-phosphate, plasma membrane, phospholipase C signaling, protein-lipid interactions
MeSH terms
Cell Membrane, Homeostasis, Membrane Proteins, Phosphatidylinositols, Phosphatidylinositol 4,5-Diphosphate, Lipoylation

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