Lipid phosphate phosphatases form homo- and hetero-oligomers : catalytic competency, subcellular distribution and function

Long, J.S. and Pyne, N.J. and Pyne, S. (2008) Lipid phosphate phosphatases form homo- and hetero-oligomers : catalytic competency, subcellular distribution and function. Biochemical Journal, 411 (2). pp. 371-377. ISSN 0264-6021 (https://doi.org/10.1042/BJ20071607)

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Abstract

Lipid phosphate phosphatases (LPP1-LPP3) have been topographically modelled as monomers (molecular mass of 31-36 kDa) composed of six transmembrane domains and with the catalytic site facing the extracellular side of the plasma membrane or the luminal side of intracellular membranes. The catalytic motif has three conserved domains, termed C1, C2 and C3. The C1 domain may be involved in substrate recognition, whereas C2 and C3 domains appear to participate in the catalytic dephosphorylation of the substrate. We have obtained three lines of evidence to demonstrate that LPPs exist as functional oligomers. First, we have used recombinant expression and immunoprecipitation analysis to demonstrate that LPP1, LPP2 and LPP3 form both homo- and hetero-oligomers. Secondly, large LPP oligomeric complexes that are catalytically active were isolated using gel-exclusion chromatography. Thirdly, we demonstrate that catalytically deficient guinea-pig FLAG-tagged H223L LPP1 mutant can form an oligomer with wild-type LPP1 and that wild-type LPP1 activity is preserved in the oligomer. These findings suggest that, in an oligomeric arrangement, the catalytic site of the wild-type LPP can function independently of the catalytic site of the mutant LPP. Finally, we demonstrate that endogenous LPP2 and LPP3 form homo- and hetero-oligomers, which differ in their subcellular localization and which may confer differing spatial regulation of phosphatidic acid and sphingosine 1-phosphate signalling.

ORCID iDs

Long, J.S., Pyne, N.J. ORCID logoORCID: https://orcid.org/0000-0002-5657-4578 and Pyne, S. ORCID logoORCID: https://orcid.org/0000-0002-6608-9584;
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