Phospholipase D: molecular and cell biology of a novel gene family

Abstract

Interaction of extracellular-signal molecules with cell-surface receptors often activates a phospholipase D (PLD)-mediated hydrolysis of phosphatidylcholine and other phospholipids, generating phosphatidic acid. The activation of PLD is believed to play an important role in the regulation of cell function and cell fate. Multiple PLD activities were characterized in eukaryotic cells, and, more recently, several PLD genes have been cloned. A PLD gene superfamily, defined by a number of structural domains and sequence motifs, also includes phosphatidyltransferases and certain phosphodiesterases. Among the eukaryotic PLD genes are those from mammals, nematodes, fungi and plants. The present review focuses on the structure, localization, regulation and possible functions of cloned mammalian and yeast PLDs. In addition, an overview of plant PLD genes, and of several distinct PLD activities that have not yet been cloned, is provided. Emerging evidence from recent work employing new molecular tools indicates that different PLD isoforms are localized in distinct cellular organelles, where they are likely to serve diverse functions in signal transduction, membrane vesicle trafficking and cytoskeletal dynamics.

Molecular diversity of phospholipase D in angiosperms

“…Using the cloned PLDs from Arabidopsis and other organisms we conducted exhaustive BLAST searches of the Arabidopsis sequences available from GenBank and found 12 genes from the eukaryotic PC-PLD family, five of them not yet recorded in the literature. All genes found code for proteins containing all the conserved sequence motifs characteristic of eukaryotic PLDs, including two copies of the invariant catalytic HxKxxxxD motif [1], suggesting that all probably posses the genuine PLD enzymatic activity (thougt this must be proven experimentally). The catalytic HxKxxxxD motif is shared also by other proteins put together with the eukaryotic PLDs into the PLD superfamily [14], we however did not identify any other members of the superfamily in Arabidopsis besides the 12 PC-PLDs.…”

“…2), but within the core of the enzyme several highly conserved regions shared by all PLDs have been recognised [1,6]. Among these, the most important are two copies of HxKxxxxD (or HKD) motif (Fig.…”

“…Animal and fungal PLDs are not directly dependent on Ca 2+ [1], and the same is likely also for plant PXPH-PLDs. On the other hand, most (but perhaps not all, see below) C2-PLDs will exhibit dependence on and regulation by Ca 2+ , as the C2 domains usually bind phospholipids in a Ca 2+ -dependent manner [26].…”

“…is a ubiquitous eukaryotic enzyme participating in various cellular processes (for a review see [1,2]). Biochemically distinct types of PLDs have been described, but only two, the mammalian glycosylphosphatidylinositol-specific PLD (GPI-PLD) and a family usually referred to as phosphatidylcholine-specific PLD (PC-PLD), have been characterised also on the molecular level.…”

Hepatic stellate cells: role in microcirculation and pathophysiology of portal hypertension

“…Stimulation of PKC results in activation of PLD and production of the second messenger phosphatidic acid (PA). 49 Addition of exogenous PLD or PA to quiescent fibroblasts elicits the formation of actin stress fibres and PLD mediates PA induced stress fibre formation in these cells. 50 51 Moreover, PLD colocalises with F-actin and three proteins, vinculin, talin, and α-actinin, found on the cytoplasmic face of focal adhesions suggesting a role in the assembly/regulation of these structures.…”