Plentiful PtdIns5P from scanty PtdIns(3,5)P2 or from ample PtdIns? PIKfyve‐dependent models: Evidence and speculation (response to: DOI 10.1002/bies.201300012)

• Published in: BioEssays Vol. 37; no. 3; pp. 267 - 277
• Main Authors: Shisheva, Assia, Sbrissa, Diego, Ikonomov, Ognian
• Format: Journal Article
• Language: English
• Published: United States Published for ICSU Press by Cambridge University Press 01.03.2015; Blackwell Publishing Ltd; Wiley Subscription Services, Inc
• Subjects: 3-phosphatases; 5)P2; 5)P2-PtdIns3P conversion; Animals; direct PtdIns5P synthesis; Humans; hydrolysis; mammals; Phosphatidylinositol Phosphates - genetics; Phosphatidylinositol Phosphates - metabolism; phosphoinositides; PIKfyve; PtdIns; PtdIns(3,5)P2; PtdIns(3,5)P2‐PtdIns3P conversion; PtdIns3P; Signal Transduction - genetics; 3-phosphatases; PIKfyve; PtdIns(3,5)P2-PtdIns3P conversion; PtdIns(3,5)P2; PtdIns3P; direct PtdIns5P synthesis; phosphoinositides
• ISSN: 0265-9247; 1521-1878; 1521-1878
• DOI: 10.1002/bies.201400129

Recently, we have presented data supporting the notion that PIKfyve not only produces the majority of constitutive phosphatidylinositol 5‐phosphate (PtdIns5P) in mammalian cells but that it does so through direct synthesis from PtdIns. Another group, albeit obtaining similar data, suggests an alternative pathway whereby the low‐abundance PtdIns(3,5)P₂undergoes hydrolysis by unidentified 3‐phosphatases, thereby serving as a precursor for most of PtdIns5P. Here, we review the experimental evidence supporting constitutive synthesis of PtdIns5P from PtdIns by PIKfyve. We further emphasize that the experiments presented in support of the alternative pathway are also compatible with a direct mechanism for PIKfyve‐catalyzed synthesis of PtdIns5P. While agreeing with the authors that constitutive PtdIns5P could theoretically be produced from PtdIns(3,5)P₂by 3‐dephosphorylation, we argue that until direct evidence for such an alternative pathway is obtained, we should adhere to the existing experimental evidence and quantitative considerations, which favor direct PIKfyve‐catalyzed synthesis for most constitutive PtdIns5P.