Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2012 Feb;204(2):219-26.
doi: 10.1111/j.1748-1716.2011.02298.x. Epub 2011 May 28.

Mammalian phospholipase D physiological and pathological roles

X Peng  1 , M A Frohman
Affiliations
Review

Mammalian phospholipase D physiological and pathological roles

X Peng et al. Acta Physiol (Oxf). 2012 Feb.

Abstract

Phospholipase D (PLD), a superfamily of signalling enzymes that most commonly generate the lipid second messenger phosphatidic acid, is found in diverse organisms from bacteria to humans and functions in multiple cellular pathways. Since the early 1980s when mammalian PLD activities were first described, most of the important insights concerning PLD function have been gained from studies on cellular models. Reports on physiological and pathophysiological roles for members of the mammalian PLD superfamily are now starting to emerge from genetic models. In this review, we summarize recent findings on PLD functions in these model systems, highlighting newly appreciated connections of the superfamily to cancer, neuronal pathophysiology, cardiovascular topics, spermatogenesis and infectious diseases.

PubMed Disclaimer

Conflict of interest statement

Conflicts of Interest

The authors do not declare any conflicts of interest.

Figures

Fig. 1
Fig. 1
A. signaling lipid pathway. PA can be generated via hydrolysis of PC or cardiolipin by PLD or MitoPLD, respectively. Once generated, the PA can be converted to DAG by Lipid Phosphatases (e.g. Lipin) or to LPA by PLA2 (phospholipase A2). B. Cartoon schematic of mammalian PLDs. PX domain (PHOX domain) and PH domain (Pleckstrin domain) mediate protein and lipid binding; HKD domain (HxKxxxxD, x is any amino acid)defines and mediates the catalytic reaction; PIP2 binding domain; Loop domain in PLD1 may function in autoinhibition of PLD1 activity; TM (transmembrane domain) is found in MitoPLD and functions to anchor the protein into the outer surface of mitochondria; RGV domain is enriched in basic amino acids that may interact with membrane surfaces or partner proteins.
Fig. 2
Fig. 2
Physiological and Pathophysiological Roles for PLD family members. See text for details.
See this image and copyright information in PMC

References

    1. Bi K, Roth MG, Ktistakis NT. Phosphatidic acid formation by phospholipase D is required for transport from the endoplasmic reticulum to the Golgi complex. Curr Biol. 1997;7:301–307. - PubMed
    1. Brandenburg LO, Konrad M, Wruck C, Koch T, Pufe T, Lucius R. Involvement of formyl-peptide-receptor-like-1 and phospholipase D in the internalization and signal transduction of amyloid beta 1–42 in glial cells. Neurosci. 2008;156:266–276. - PubMed
    1. Brown FD, Thompson N, Saqib KM, Clark JM, Powner D, Thompson NT, Solari R, Wakelam MJ. Phospholipase D1 localises to secretory granules and lysosomes and is plasma-membrane translocated on cellular stimulation. Curr Biol. 1998;8:835–838. - PubMed
    1. Cai D, Netzer WJ, Zhong M, Lin Y, Du G, Frohman M, Foster DA, Sisodia SS, Xu H, Gorelick FS, Greengard P. Presenilin-1 uses phospholipase D1 as a negative regulator of beta-amyloid formation. Proc Natl Acad Sci U S A. 2006a;103:1941–1946. - PMC - PubMed
    1. Cai D, Zhong M, Wang R, Netzer WJ, Shields D, Zheng H, Sisodia SS, Foster DA, Gorelick FS, Xu H, Greengard P. Phospholipase D1 corrects impaired betaAPP trafficking and neurite outgrowth in familial Alzheimer’s disease-linked presenilin-1 mutant neurons. Proc Natl Acad Sci U S A. 2006b;103:1936–1940. - PMC - PubMed

Publication types