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Comment
. 2019 Jul 1;218(7):2082-2083.
doi: 10.1083/jcb.201906022. Epub 2019 Jun 12.

The enemy of my enemy: PTEN and PLCXD collude to fight endosomal PtdIns(4,5)P2

Steven J Del Signore  1 , Avital A Rodal  2
Affiliations
Comment

The enemy of my enemy: PTEN and PLCXD collude to fight endosomal PtdIns(4,5)P2

Steven J Del Signore et al. J Cell Biol. .

Abstract

Loss of the phosphoinositide 5-phosphatase OCRL causes accumulation of PtdIns(4,5)P2 on membranes and, ultimately, Lowe syndrome. In this issue, Mondin et al. (2019. J. Cell Biol. https://doi.org/10.1083/jcb.201805155) discover that a surprising partnership between PTEN and the phospholipase PLCXD can compensate for OCRL to suppress endosomal PtdIns(4,5)P2 accumulation.

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Figures

Figure 1.
Figure 1.
PTEN and PLCXD counteract endosomal PIP2 accumulation in the absence of OCRL. (A) Schematic of PtdIns(4,5)P2 metabolism: OCRL and PLC directly decrease PtdIns(4,5)P2 levels, while PTEN canonically increases PtdIns(4,5)P2 by dephosphorylation of PtdIns(3,4,5)P3. (B) In healthy cells, OCRL and PTEN–PLCXD prevent PtdIns(4,5)P2 accumulation on endosomes. (C) OCRL-deficient cells accumulate PtdIns(4,5)P2 on endosomes. (D) Activation of the PTEN–PLCXD pathway by exogenous PTEN or PLCXD activation restores normal endosomal PtdIns(4,5)P2 levels.
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