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Roles of PIKfyve in multiple cellular pathways.

Abstract
Phosphoinositide signaling lipids are crucial for eukaryotes and regulate many aspects of cell function. These signaling molecules are difficult to study because they are extremely low abundance. Here, we focus on two of the lowest abundance phosphoinositides, PI(3,5)P2 and PI(5)P, which play critical roles in cellular homeostasis, membrane trafficking and transcription. Their levels are tightly regulated by a protein complex that includes PIKfyve, Fig4 and Vac14. Importantly, mutations in this complex that decrease PI(3,5)P2 and PI(5)P are linked to human diseases, especially those of the nervous system. Paradoxically, PIKfyve inhibitors which decrease PI(3,5)P2 and PI(5)P, are currently being tested for some neurodegenerative diseases, as well as other diverse diseases including some cancers, and as a treatment for SARS-CoV2 infection. A more comprehensive picture of the pathways that are regulated by PIKfyve will be critical to understand the roles of PI(3,5)P2 and PI(5)P in normal human physiology and in disease.
AuthorsPilar Rivero-Ríos, Lois S Weisman
JournalCurrent opinion in cell biology (Curr Opin Cell Biol) Vol. 76 Pg. 102086 (06 2022) ISSN: 1879-0410 [Electronic] England
PMID35584589 (Publication Type: Journal Article, Review, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
CopyrightCopyright © 2022 Elsevier Ltd. All rights reserved.
Chemical References
  • Flavoproteins
  • Intracellular Signaling Peptides and Proteins
  • Membrane Proteins
  • Phosphatidylinositol Phosphates
  • Phosphatidylinositols
  • RNA, Viral
  • VAC14 protein, human
  • PIKFYVE protein, human
  • FIG4 protein, human
  • Phosphoric Monoester Hydrolases
Topics
  • Flavoproteins (metabolism)
  • Humans
  • Intracellular Signaling Peptides and Proteins
  • Membrane Proteins (metabolism)
  • Phosphatidylinositol 3-Kinases (metabolism)
  • Phosphatidylinositol Phosphates (metabolism)
  • Phosphatidylinositols
  • Phosphoric Monoester Hydrolases
  • RNA, Viral
  • SARS-CoV-2
  • COVID-19 Drug Treatment

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