Abstract
The field of inositol signaling has expanded greatly in recent years. Given the many reviews on phosphoinositide kinases, we have chosen to restrict our discussion to inositol lipid hydrolysis focused on the phosphatases and a brief mention of the lipase isoforms. We also discuss recent discoveries that link mutations in phosphoinositide phosphatases to disease.
Highlights
PATHOLOGY RESULTING FROM DERANGED INOSITOL SIGNALINGThe significance of inositol signaling with respect to human health is highlighted by the fact that mutations in enzymes of inositol signaling cause numerous diseases and pathologies (Table 1)
The field of inositol signaling has expanded greatly in recent years
The inositol phospholipids are interconverted by kinases and phosphatases as well as cleaved by phospholipase C (PLC) enzymes
Summary
The significance of inositol signaling with respect to human health is highlighted by the fact that mutations in enzymes of inositol signaling cause numerous diseases and pathologies (Table 1). Mutation of the gene encoding a PIP2 5-phosphatase (5-ptase) (OCRL) in humans causes a severe X-linked disorder called Lowe syndrome, while the OCRL knockout mouse has no phenotype [1]. MTMR1-8 have 3-phosphatase activity, while MTMR9-13 lack the catalytic active site cysteine residue. The inactive subunits partner with active MTM proteins to form heteromers, which increase enzyme activity and in some cases alter cellular location. The importance of the inactive subunits is illustrated by the finding that mutations of MTMR13, the inactive partner of MTMR2, cause the same disorder as mutation of the active partner. Mutations in factor-induced gene 4 (FIG4) in mice cause the pale tremor mouse syndrome, while mutation of the human ortholog causes a form of Charcot Marie Tooth disease. Mutations that truncate the last 18 amino acids result in MORM syndrome, while mutations in the catalytic domain cause Joberts syndrome
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