Phospholipase C and D regulation of Src, calcium release and membrane fusion during Xenopus laevis development

Abstract

This review emphasizes how lipids regulate membrane fusion and the proteins involved in three developmental stages: oocyte maturation to the fertilizable egg, fertilization and during first cleavage. Decades of work show that phosphatidic acid (PA) releases intracellular calcium, and recent work shows that the lipid can activate Src tyrosine kinase or phospholipase C during Xenopus fertilization. Numerous reports are summarized to show three levels of increase in lipid second messengers inositol 1,4,5-trisphosphate and sn 1,2-diacylglycerol (DAG) during the three different developmental stages. In addition, possible roles for PA, ceramide, lysophosphatidylcholine, plasmalogens, phosphatidylinositol 4-phosphate, phosphatidylinositol 5-phosphate, phosphatidylinositol 4,5-bisphosphate, membrane microdomains (rafts) and phosphatidylinositol 3,4,5-trisphosphate in regulation of membrane fusion (acrosome reaction, sperm-egg fusion, cortical granule exocytosis), inositol 1,4,5-trisphosphate receptors, and calcium release are discussed. The role of six lipases involved in generating putative lipid second messengers during fertilization is also discussed: phospholipase D, autotaxin, lipin1, sphingomyelinase, phospholipase C, and phospholipase A2. More specifically, proteins involved in developmental events and their regulation through lipid binding to SH3, SH4, PH, PX, or C2 protein domains is emphasized. New models are presented for PA activation of Src (through SH3, SH4 and a unique domain), that this may be why the SH2 domain of PLCγ is not required for Xenopus fertilization, PA activation of phospholipase C, a role for PA during the calcium wave after fertilization, and that calcium/calmodulin may be responsible for the loss of Src from rafts after fertilization. Also discussed is that the large DAG increase during fertilization derives from phospholipase D production of PA and lipin dephosphorylation to DAG.

Lipid composition of the cancer cell membrane

“…This promotes DGK trafficking to the plasma membrane, which eventually induces PA biosynthesis (Purow 2015). DGK may be activated by pathogen-induced enhanced phospholipase (PLC) activity as well (Stith 2015). PA biosynthesis is also catalysed by PLD which activity is G-protein-dependent (Brandenburg 2014).…”

Phosphatidic acid in membrane rearrangements

“…Phosphatidic acid, LPA and DAG are involved in many membrane fusion and membrane fission events, such as fission of Golgi membranes , fission during endocytic transport , vacuole fission and fusion , mitochondrial dynamics , exocytosis , vesicle‐vesicle fusion , myoblast fusion , osteoclast fusion , membrane fusion during sporulation , membrane fusion during fertilization . Fusion of PA‐containing vesicles was studied in Refs .…”

“…Phosphatidic acid, LPA and DAG are involved in many membrane fusion and membrane fission events, such as fission of Golgi membranes [140,162,163,[165][166][167][168][169], fission during endocytic transport [170,171], vacuole fission [172] and fusion [132,147,[173][174][175], mitochondrial dynamics [17,40,95,[176][177][178][179][180][181][182][183][184][185], exocytosis [30,40,76,79,125,[186][187][188][189][190][191][192][193][194], vesicle-vesicle fusion [164], myoblast fusion [195,196], osteoclast fusion [197], membrane fusion during sporulation [198][199][200][201], membrane fusion during fertilization [202,203]. Fusion of PA-containing vesicles was studied in Refs [87,…”

Phospholipase D and phosphatidic acid in the biogenesis and cargo loading of extracellular vesicles

“…Indeed, nSMase2 has also been proposed to interact with PA (54,55), and this binding activity could support nSMase2 targeting (and ceramide formation) to MVBs (54). Interestingly, PA can interact with SRC through the SH4, unique lipid binding region (ULRB), and SH3 domains, stimulating its activation by favoring the open conformation (56). In turn, in cells like MCF-7, SRC can activate PLD2 by phosphorylating its tyrosine 511 (57).…”