Vps34 is a phosphatidylinositol 3-kinase, not a phosphoinositide 3-kinase

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Meijer, A.J.; Klionsky, D.J.

DOI

10.4161/auto.7.6.14873

Publication date

2011

Document Version

Final published version

Published in

Autophagy

Link to publication

Citation for published version (APA):

Meijer, A. J., & Klionsky, D. J. (2011). Vps34 is a phosphatidylinositol 3-kinase, not a

phosphoinositide 3-kinase. Autophagy, 7(6), 563-564. https://doi.org/10.4161/auto.7.6.14873

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www.landesbioscience.com Autophagy 563

Editor’s cornEr

There seems to be some confusion regard-ing the namregard-ing of enzymes that phosphor-ylate certain lipids. In particular, we are referring to the lipid phosphatidylinositol and to phosphoinositides. Inositides are inositol-containing derivatives of phatidic acid (Fig. 1). The term phos-phoinositide indicates that one or more of the hydroxyl groups of phosphatidylinosi-tol is esterified with inorganic phosphate. Phosphatidylinositol is an inositide, but it is not a phosphoinositide, whereas phos-phatidylinositol 3-phosphate (phospha-tidylinositol that is phosphorylated on the three hydroxyl group of inositol) is a phosphoinositide (Fig. 1). In addition to phophatidylinositol 3-phosphate, the lip-ids phosphatidylinositol 3,4-bisphosphate, phosphatidylinositol 3,5-bisphosphate and phosphatidylinositol 3,4,5-trisphosphate are all phosphoinositides.

There is a single enzyme that converts phosphatidylinositol to phosphatidylino-sitol 3-phosphate, and that is Vps34. Furthermore, Vps34 only phosphorylates phosphatidylinositol, and does not act on other substrates. Thus, Vps34 is not a phosphoinositide kinase, but rather is a phosphatidylinositol kinase that phos-phorylates the three hydroxyl group, making it in particular a phosphatidylino-sitol 3-kinase. In contrast, Vps34 is not a phosphoinositide 3-kinase, because its substrate, phosphatidylinositol, is not a phosphoinositide. At this point it might be worth considering, albeit briefly, the origin of these terms. That is, the end-ing “-ide” refers to a chemical compound derived from or related to another such compound, or indicating one of a class

Vps34 is a phosphatidylinositol 3-kinase,

not a phosphoinositide 3-kinase

Alfred J. Meijer1_{and daniel J. Klionsky}2,_*

1_{University of Amsterdam; Academic Medical center; department of Medical Biochemistry; Amsterdam, the netherlands;}2_{University of Michigan; Life sciences institute;} Ann Arbor, Mi UsA

Key words: autophagy, lipids, lysosome, phagophore, phosphatidylinositol, sequestration, stress, vacuole

of compounds. Thus, a phosphoinosit-ide is related to phosphatidylinositol, and phosphatidylinositol 3 phosphate is one of a class of phosphoinositides. The suf-fix “-ol” is used in the names of chemical derivatives representing alcohol (inositol is a sugar alcohol; Fig. 1).

When you see the abbreviation “PI3K” it is not clear whether the author is refer-ring to a phosphoinositide 3-kinase or a phosphatidylinositol 3-kinase. In contrast, “PtdIns3K” makes it quite clear that the enzyme is acting upon phosphatidylino-sitol. Perhaps we are being obsessive, but

when it comes to Vps34 we think people should refer to it as a phosphatidylinositol 3-kinase because they are discussing the generation of phosphatidylinositol 3-phos-phate or PtdIns(3)P, which is one of the lipids that we tend to be most concerned about with regard to macroautophagy. This is the reason that Autophagy uses the abbreviation “PtdIns3K” as the stan-dard for the enzyme complex contain-ing Vps34. Furthermore, you will not go wrong if you describe a phosphoinositide kinase such as Fab1 as a phosphatidylino-sitol 3-phosphate 5-kinase (PtdIns(3)

Figure 1. chemical structures of inositol, phosphatidic acid, phosphatidylinositol (an inositide,

but not a phosphoinositide) and phosphatidylinositol 3-phosphate (a phosphoinositide).

*Correspondence to: Daniel J. Klionsky; Email: klionsky@umich.edu Submitted: 01/18/11; Accepted: 01/20/11

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564 Autophagy Volume 7 issue 6

P 5-kinase), for example, whereas you run the risk of incorrectly referring to an enzyme such as Vps34 as a phosphoinosit-ide kinase.

There is one additional issue, and that concerns the distinction between the different classes of phosphatidylino-sitol kinases, and in particular the class I and class III enzymes. In this case, many people refer to the PI3KC3, which is a short and handy name, except when you

consider that the official gene name in humans is “PIK3C3,” with the “3” and the “K” transposed, and both of these suffer from the problem of not making it clear whether we are really referring to a phosphatidylinositol 3-kinase or a phosphoinositide 3-kinase. Again, the class III enzyme that generates phospha-tidylinositol 3-phosphate is not a phos-phoinositide 3-kinase. In contrast, the enzyme that phosphorylates PtdIns(4,5)

P₂ to PtdIns(3,4,5)P₃ can be correctly referred to as a phosphoinositide-3- kinase, but the substrate specificity is still not indicated. Therefore, Autophagy will use “PtdIns3KC3” to refer to the class III enzyme Vps34 when necessary, as this makes it clear that the substrate is phosphatidylinositol 3-phosphate.

We certainly hope this clears up any confusion.