The emerging physiological roles of the glycerophosphodiesterase family

Abstract

The glycerophosphodiester phosphodiesterases are evolutionarily conserved proteins that have been linked to several patho/physiological functions, comprising bacterial pathogenicity and mammalian cell proliferation or differentiation. The bacterial enzymes do not show preferential substrate selectivities among the glycerophosphodiesters, and they are mainly dedicated to glycerophosphodiester hydrolysis, producing glycerophosphate and alcohols as the building blocks that are required for bacterial biosynthetic pathways. In some cases, this enzymatic activity has been demonstrated to contribute to bacterial pathogenicity, such as with Hemophilus influenzae. Mammalian glyerophosphodiesterases have high substrate specificities, even if the number of potential physiological substrates is continuously increasing. Some of these mammalian enzymes have been directly linked to cell differentiation, such as GDE2, which triggers motor neuron differentiation, and GDE3, the enzymatic activity of which is necessary and sufficient to induce osteoblast differentiation. Instead, GDE5 has been shown to inhibit skeletal muscle development independent of its enzymatic activity.

New Members of the Mammalian Glycerophosphodiester Phosphodiesterase Family

“…GP-PDEs are widely found in prokaryotes and eukaryotes, although their distinct physiological roles remain unclear, particularly in eukaryotes (5,6). Mammalian GP-PDEs have more selective substrate specificities toward GPs, which prompts us to assume that their enzymatic activities are mainly devoted to modulate GroPIns and/or GroPCho concentrations.…”

“…GPs are produced via phospholipase A 1 and phospholipase A 2 activities, and they are degraded by GP phosphodiesterases (GP-PDEs) (1)(2)(3)(4). Six mammalian GP-PDEs were previously isolated, and investigations have been carried out to explore their physiological significance (5,6). In renal cells, GDE2 contributes to osmotic regulation as a GroPCho phosphodiesterase, which is supported by increasing evidence that GroPCho acts as an organic osmolyte (7)(8)(9).…”

“…Indeed, GroPIns has been shown to regulate cell growth in thyroid cells (4), and induction of its hydrolysis through GDE3 expression results in reduced osteoblast proliferation and the appearance of markers of osteoblast differentiation (12). Thus, mammalian GP-PDEs have an intriguing feature; they show restricted substrate specificities, which prompted us to consider the possibility that mammalian GP-PDEs modulate GroPCho and/or GroPIns concentrations, because these intracellular GPs are increasingly recognized as bioactive molecules that are involved in a variety of cellular events (6). Recently, Simon and Cravatt (13,14) reported that GDE1 is involved in the production of anandamide from glycerophospho-N-arachidonoylethanolamine in the nervous system.…”

GPI-AP release in cellular, developmental, and reproductive biology

“…Seven homologs (GDE1-7) are conserved in mice and humans. The physiological roles of the GDE family were recently reviewed ( 60 ). GDE2 (also known as GDPD5) has six transmembrane domains and an extracellular GDPD domain ( 61 ).…”

The Baseplate of Lactobacillus delbrueckii Bacteriophage Ld17 Harbors a Glycerophosphodiesterase

“…all domains of life (from bacteria to humans) (1). During degradation of the bacterial and eukaryotic cell membrane, the glycerophospholipid building blocks are first deacylated by phospholipases A 1 and A 2 , resulting in the formation of glycerophosphodiesters.…”