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Signal transduction of fertilization in frog eggs and anti-apoptotic mechanism in human cancer cells: common and specific functions of membrane microdomains.

Sato K - Open Biochem J (2008)

Bottom Line: Moreover, fertilization of Xenopus eggs involves proteolytic cleavage of the extracellular part and subsequent phosphorylation of a cytoplasmic tyrosine residue of uroplakin III, an egg membrane microdomain-associated protein.Therefore, it is assumed that uroplakin III serves an integral part of signal transduction in fertilization of Xenopus.Namely, in human bladder carcinoma cells, cooperation of uroplakin III and Src, both of which localize to the membrane microdomains, allows cells to escape from apoptotic cell death and proliferate under culture conditions deprived of serum.

View Article: PubMed Central - PubMed

Affiliation: Laboratory of Cell and Developmental Biology, Department of Biotechnology, Faculty of Engineering, Kyoto Sangyo University, Kamigamo-Motoyama, Kyoto 603-8555, Japan. kksato@cc.kyoto-su.ac.jp

ABSTRACT
Membrane microdomains or lipid/membrane rafts are distinct areas on the plasma membranes, where a specific subset of lipids (e.g. cholesterol, sphingolipids) and proteins (e.g. glycosylphosphatidylinositol-anchored proteins, growth factor receptor/kinases) are getting together and functioning for several aspects of cellular functions. Our recent investigation has revealed that fertilization of African clawed frog, Xenopus laevis, requires cholesterol-dependent nature of egg membrane microdomains. Moreover, fertilization of Xenopus eggs involves proteolytic cleavage of the extracellular part and subsequent phosphorylation of a cytoplasmic tyrosine residue of uroplakin III, an egg membrane microdomain-associated protein. Protease activity toward uroplakin III seems to be derived from fertilizing sperm, while phosphorylation of uroplakin III seems to be catalyzed by the egg tyrosine kinase Src, whose activation is required for cytoplasmic rearrangement of fertilized eggs; so-called 'egg activation'. Therefore, it is assumed that uroplakin III serves an integral part of signal transduction in fertilization of Xenopus. Our more recent study on human cancer cells has revealed that a similar but distinct scheme of signal transduction operates in anti-apoptotic growth of cells. Namely, in human bladder carcinoma cells, cooperation of uroplakin III and Src, both of which localize to the membrane microdomains, allows cells to escape from apoptotic cell death and proliferate under culture conditions deprived of serum. In this review, I briefly introduce about biology of fertilization and cancer, and then present and discuss our experimental data on general importance and specific features of membrane microdomains in Xenopus fertilization and anti-apoptosis in human bladder carcinoma cells.

No MeSH data available.


Related in: MedlinePlus

Study of fertilization signaling focusing on structure and function of egg plasma membrane microdomains. (A) Schematic drawing of preparation of membrane microdomains from Xenopus eggs, which are unfertilized, fertilized, or artificially activated (parthenogenetically activated), and its utility in functional analysis. (B) Schematic diagram showing a series of events that operates during early phase of fertili-zation of Xenopus eggs. Sperm-induced egg activation may involve proteolytic cleavage of the egg membrane microdomain-associated uro-plakin III, catalyzed by sperm-derived protease. Uroplakin III is in association with uroplakin Ib, a tetraspanin molecule that supports the localization of uroplakin III to membrane microdomains. The uroplakin III-uroplakin Ib complex is involved in negative regulation of cyto-plasmic tyrosine kinase Src, and proteolytic cleavage of uroplakin III may lead to up-regulation of Src by unknown mechanism. Activated Src phosphorylates and activates PLC,γ which in turn promotes IP3 production and Ca2+transient.Src may also phosphorylate intact uro-plakin III, although its physiological importance has not yet been demonstrated
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Figure 2: Study of fertilization signaling focusing on structure and function of egg plasma membrane microdomains. (A) Schematic drawing of preparation of membrane microdomains from Xenopus eggs, which are unfertilized, fertilized, or artificially activated (parthenogenetically activated), and its utility in functional analysis. (B) Schematic diagram showing a series of events that operates during early phase of fertili-zation of Xenopus eggs. Sperm-induced egg activation may involve proteolytic cleavage of the egg membrane microdomain-associated uro-plakin III, catalyzed by sperm-derived protease. Uroplakin III is in association with uroplakin Ib, a tetraspanin molecule that supports the localization of uroplakin III to membrane microdomains. The uroplakin III-uroplakin Ib complex is involved in negative regulation of cyto-plasmic tyrosine kinase Src, and proteolytic cleavage of uroplakin III may lead to up-regulation of Src by unknown mechanism. Activated Src phosphorylates and activates PLC,γ which in turn promotes IP3 production and Ca2+transient.Src may also phosphorylate intact uro-plakin III, although its physiological importance has not yet been demonstrated

Mentions: The term “membrane microdomains” or “membrane/lipid rafts” denotes a distinct area or micro-segment on the plasma membranes, where a specific subset of proteins and membrane lipids are getting together and working for certain cellular functions [53-59]. It is sometimes called as “cavelolae microdomains” or more simply “caveolae”, when it involves invaginated membrane structures containing caveolin, a membrane-spanning protein [56]. With experimental basis, membrane microdomains are also called as “detergent-insoluble membrane (DIM)” or “detergent-resistant membranes (DRM)” [53,57,58]. Such detergent-insoluble or resistant nature of membrane microdomains is due to an enrichment of cholesterol and saturated fatty acids that constitute liquid-ordered membranes. Conventional preparation of membrane microdomains involves extraction of cell samples with Triton-X-100 (or other non-ionic detergents)-containing buffer at low temperature, followed by fractionation of the extracts with discontinuous sucrose gradient ultracentrifugation (Fig. 2a). The resulting fractions containing low-density, detergent-insoluble materials are collected as membrane microdomains. For further details of technical issues and merits of focused approach on egg membrane microdomains in fertilization study, please refer to other literatures [60,61].


Signal transduction of fertilization in frog eggs and anti-apoptotic mechanism in human cancer cells: common and specific functions of membrane microdomains.

Sato K - Open Biochem J (2008)

Study of fertilization signaling focusing on structure and function of egg plasma membrane microdomains. (A) Schematic drawing of preparation of membrane microdomains from Xenopus eggs, which are unfertilized, fertilized, or artificially activated (parthenogenetically activated), and its utility in functional analysis. (B) Schematic diagram showing a series of events that operates during early phase of fertili-zation of Xenopus eggs. Sperm-induced egg activation may involve proteolytic cleavage of the egg membrane microdomain-associated uro-plakin III, catalyzed by sperm-derived protease. Uroplakin III is in association with uroplakin Ib, a tetraspanin molecule that supports the localization of uroplakin III to membrane microdomains. The uroplakin III-uroplakin Ib complex is involved in negative regulation of cyto-plasmic tyrosine kinase Src, and proteolytic cleavage of uroplakin III may lead to up-regulation of Src by unknown mechanism. Activated Src phosphorylates and activates PLC,γ which in turn promotes IP3 production and Ca2+transient.Src may also phosphorylate intact uro-plakin III, although its physiological importance has not yet been demonstrated
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2570554&req=5

Figure 2: Study of fertilization signaling focusing on structure and function of egg plasma membrane microdomains. (A) Schematic drawing of preparation of membrane microdomains from Xenopus eggs, which are unfertilized, fertilized, or artificially activated (parthenogenetically activated), and its utility in functional analysis. (B) Schematic diagram showing a series of events that operates during early phase of fertili-zation of Xenopus eggs. Sperm-induced egg activation may involve proteolytic cleavage of the egg membrane microdomain-associated uro-plakin III, catalyzed by sperm-derived protease. Uroplakin III is in association with uroplakin Ib, a tetraspanin molecule that supports the localization of uroplakin III to membrane microdomains. The uroplakin III-uroplakin Ib complex is involved in negative regulation of cyto-plasmic tyrosine kinase Src, and proteolytic cleavage of uroplakin III may lead to up-regulation of Src by unknown mechanism. Activated Src phosphorylates and activates PLC,γ which in turn promotes IP3 production and Ca2+transient.Src may also phosphorylate intact uro-plakin III, although its physiological importance has not yet been demonstrated
Mentions: The term “membrane microdomains” or “membrane/lipid rafts” denotes a distinct area or micro-segment on the plasma membranes, where a specific subset of proteins and membrane lipids are getting together and working for certain cellular functions [53-59]. It is sometimes called as “cavelolae microdomains” or more simply “caveolae”, when it involves invaginated membrane structures containing caveolin, a membrane-spanning protein [56]. With experimental basis, membrane microdomains are also called as “detergent-insoluble membrane (DIM)” or “detergent-resistant membranes (DRM)” [53,57,58]. Such detergent-insoluble or resistant nature of membrane microdomains is due to an enrichment of cholesterol and saturated fatty acids that constitute liquid-ordered membranes. Conventional preparation of membrane microdomains involves extraction of cell samples with Triton-X-100 (or other non-ionic detergents)-containing buffer at low temperature, followed by fractionation of the extracts with discontinuous sucrose gradient ultracentrifugation (Fig. 2a). The resulting fractions containing low-density, detergent-insoluble materials are collected as membrane microdomains. For further details of technical issues and merits of focused approach on egg membrane microdomains in fertilization study, please refer to other literatures [60,61].

Bottom Line: Moreover, fertilization of Xenopus eggs involves proteolytic cleavage of the extracellular part and subsequent phosphorylation of a cytoplasmic tyrosine residue of uroplakin III, an egg membrane microdomain-associated protein.Therefore, it is assumed that uroplakin III serves an integral part of signal transduction in fertilization of Xenopus.Namely, in human bladder carcinoma cells, cooperation of uroplakin III and Src, both of which localize to the membrane microdomains, allows cells to escape from apoptotic cell death and proliferate under culture conditions deprived of serum.

View Article: PubMed Central - PubMed

Affiliation: Laboratory of Cell and Developmental Biology, Department of Biotechnology, Faculty of Engineering, Kyoto Sangyo University, Kamigamo-Motoyama, Kyoto 603-8555, Japan. kksato@cc.kyoto-su.ac.jp

ABSTRACT
Membrane microdomains or lipid/membrane rafts are distinct areas on the plasma membranes, where a specific subset of lipids (e.g. cholesterol, sphingolipids) and proteins (e.g. glycosylphosphatidylinositol-anchored proteins, growth factor receptor/kinases) are getting together and functioning for several aspects of cellular functions. Our recent investigation has revealed that fertilization of African clawed frog, Xenopus laevis, requires cholesterol-dependent nature of egg membrane microdomains. Moreover, fertilization of Xenopus eggs involves proteolytic cleavage of the extracellular part and subsequent phosphorylation of a cytoplasmic tyrosine residue of uroplakin III, an egg membrane microdomain-associated protein. Protease activity toward uroplakin III seems to be derived from fertilizing sperm, while phosphorylation of uroplakin III seems to be catalyzed by the egg tyrosine kinase Src, whose activation is required for cytoplasmic rearrangement of fertilized eggs; so-called 'egg activation'. Therefore, it is assumed that uroplakin III serves an integral part of signal transduction in fertilization of Xenopus. Our more recent study on human cancer cells has revealed that a similar but distinct scheme of signal transduction operates in anti-apoptotic growth of cells. Namely, in human bladder carcinoma cells, cooperation of uroplakin III and Src, both of which localize to the membrane microdomains, allows cells to escape from apoptotic cell death and proliferate under culture conditions deprived of serum. In this review, I briefly introduce about biology of fertilization and cancer, and then present and discuss our experimental data on general importance and specific features of membrane microdomains in Xenopus fertilization and anti-apoptosis in human bladder carcinoma cells.

No MeSH data available.


Related in: MedlinePlus