Limits...
Sweet taste receptor signaling network: possible implication for cognitive functioning.

Welcome MO, Mastorakis NE, Pereverzev VA - Neurol Res Int (2015)

Bottom Line: These receptors can sense the taste of a range of molecules and transmit the information downstream to several acceptors, modulate cell specific functions and metabolism, and mediate cell-to-cell coupling through paracrine mechanism.Recent reports indicate that sweet taste receptors are widely distributed in the body and serves specific function relative to their localization.Based on increasing evidence about the role of these receptors in the initiation and control of absorption and metabolism, and the pivotal role of metabolic (glucose) regulation in the central nervous system functioning, we propose a possible implication of sweet taste receptor signaling in modulating cognitive functioning.

View Article: PubMed Central - PubMed

Affiliation: World Scientific and Engineering Academy and Society, Ag. Ioannou Theologou 17-23, Zografou, 15773 Athens, Greece.

ABSTRACT
Sweet taste receptors are transmembrane protein network specialized in the transmission of information from special "sweet" molecules into the intracellular domain. These receptors can sense the taste of a range of molecules and transmit the information downstream to several acceptors, modulate cell specific functions and metabolism, and mediate cell-to-cell coupling through paracrine mechanism. Recent reports indicate that sweet taste receptors are widely distributed in the body and serves specific function relative to their localization. Due to their pleiotropic signaling properties and multisubstrate ligand affinity, sweet taste receptors are able to cooperatively bind multiple substances and mediate signaling by other receptors. Based on increasing evidence about the role of these receptors in the initiation and control of absorption and metabolism, and the pivotal role of metabolic (glucose) regulation in the central nervous system functioning, we propose a possible implication of sweet taste receptor signaling in modulating cognitive functioning.

No MeSH data available.


Related in: MedlinePlus

A general model of sweet taste signaling network. Sweet taste receptors possess multiple binding sites and mode of interaction for sweet molecules and they belong to class C of heterotrimeric guanine nucleotide-binding protein, G-protein [143–145]. Sweet molecules activate the G-protein by downstream signaling leading to the dissociation of the α-subunit gustducin from the βγ subunits [146, 147]. Dissociated βγ subunits of the G-protein activate phospholipase Cβ (PLCβ), leading to the formation of 1,4,5-inositol trisphosphate (IP3). IP3 is responsible for the release of Ca2+ from intracellular stores through its binding to IP3-receptor in these stores. Increase in intracellular Ca2+ activates calcium dependent kinase, monovalent selective cation channel, TRPM5 (transient receptor potential cation channel, subfamily M, member 5) [15, 44, 146], and other receptors [44, 148]. To establish the role of TRPM5 or PLCβ (type 2), Zhang et al. [4] showed that knockout of the receptor or the enzyme abolishes the sensation of taste in cells. TRPM5 may also play a role in capacitance mediated calcium entry into taste cells [147]. Modulation of purinergic signaling by taste receptor also plays useful role in taste sensation. For the initiation of purinergic release, it was recently demonstrated by Taruno et al. [148] that the voltage-gated ion channel, calcium homeostasis modulator 1 (CALHM1), is indispensable for taste-stimuli-evoked ATP release from sweet, bitter, and umami taste cells. Importantly, CALHM1 is expressed not only in sweet but also in bitter and umami taste sensing type 2 cells. Taruno et al. [148] proposed that CALHM1 is a voltage-gated ATP-release channel. Dissociated α subunit referred to as Gα-gustducin activates a phosphodiesterase (PDE) thereby decreasing intracellular cAMP levels [146, 149]. Gα-gustducin is also reported to activate adenylate cyclase (AC) to increase cAMP level [150]. According to earlier report, Clapp et al. [151] demonstrated that, compared to wild type mice, knockout of α-gustducin in the taste buds of mice resulted in high basal (unstimulated) cAMP level. The results of these authors [151] indicated that α-gustducin is necessary to maintain low level of cAMP level. Low level of cAMP is necessary to maintain the adequate signaling of Ca2+ by disinhibition of cyclic nucleotide-inhibited channels to elevate intracellular Ca2+ [38]. Changes in cAMP levels also affect other ion channels, including K+ channels. The events resulting in activation/modulation of ion channels lead to membrane depolarization and formation of action potentials. Potential-dependent release of mediators (ATP, serotonin, etc.) and peptides and calcium dependent release of peptides/biomolecules are some of the results of sweet taste receptor signaling [152]. A hallmark of sweet taste receptor signaling is the activation of transcription factors and gene expression, which might be dependent on calcium and activity dependent activation calcium dependent kinases, including the calmodulin-dependent protein kinase (CAMK). Activation of protein kinases may be achieved through other signaling pathways. It appears that sweet taste receptor signaling involves multiple activating substrates and different types and subtypes of both α-gustducin and βγ subunits of the G-protein. Although, different subtypes of sweet taste G-protein receptor subunits have been known for over a decade, their specific roles in sensing taste are not exactly clear [38, 149, 153]. For instance, Huangu et al. [149] reported the presence of β1 and γ13. The sweet taste receptor is also known to have β3 subtype subunit. For α-gustducin, Gαi-2, Gαi-3, Gα14, Gα15, Gαq, Gαs, α-transducin have been identified [38].
© Copyright Policy - open-access
Related In: Results  -  Collection


getmorefigures.php?uid=PMC4306214&req=5

fig1: A general model of sweet taste signaling network. Sweet taste receptors possess multiple binding sites and mode of interaction for sweet molecules and they belong to class C of heterotrimeric guanine nucleotide-binding protein, G-protein [143–145]. Sweet molecules activate the G-protein by downstream signaling leading to the dissociation of the α-subunit gustducin from the βγ subunits [146, 147]. Dissociated βγ subunits of the G-protein activate phospholipase Cβ (PLCβ), leading to the formation of 1,4,5-inositol trisphosphate (IP3). IP3 is responsible for the release of Ca2+ from intracellular stores through its binding to IP3-receptor in these stores. Increase in intracellular Ca2+ activates calcium dependent kinase, monovalent selective cation channel, TRPM5 (transient receptor potential cation channel, subfamily M, member 5) [15, 44, 146], and other receptors [44, 148]. To establish the role of TRPM5 or PLCβ (type 2), Zhang et al. [4] showed that knockout of the receptor or the enzyme abolishes the sensation of taste in cells. TRPM5 may also play a role in capacitance mediated calcium entry into taste cells [147]. Modulation of purinergic signaling by taste receptor also plays useful role in taste sensation. For the initiation of purinergic release, it was recently demonstrated by Taruno et al. [148] that the voltage-gated ion channel, calcium homeostasis modulator 1 (CALHM1), is indispensable for taste-stimuli-evoked ATP release from sweet, bitter, and umami taste cells. Importantly, CALHM1 is expressed not only in sweet but also in bitter and umami taste sensing type 2 cells. Taruno et al. [148] proposed that CALHM1 is a voltage-gated ATP-release channel. Dissociated α subunit referred to as Gα-gustducin activates a phosphodiesterase (PDE) thereby decreasing intracellular cAMP levels [146, 149]. Gα-gustducin is also reported to activate adenylate cyclase (AC) to increase cAMP level [150]. According to earlier report, Clapp et al. [151] demonstrated that, compared to wild type mice, knockout of α-gustducin in the taste buds of mice resulted in high basal (unstimulated) cAMP level. The results of these authors [151] indicated that α-gustducin is necessary to maintain low level of cAMP level. Low level of cAMP is necessary to maintain the adequate signaling of Ca2+ by disinhibition of cyclic nucleotide-inhibited channels to elevate intracellular Ca2+ [38]. Changes in cAMP levels also affect other ion channels, including K+ channels. The events resulting in activation/modulation of ion channels lead to membrane depolarization and formation of action potentials. Potential-dependent release of mediators (ATP, serotonin, etc.) and peptides and calcium dependent release of peptides/biomolecules are some of the results of sweet taste receptor signaling [152]. A hallmark of sweet taste receptor signaling is the activation of transcription factors and gene expression, which might be dependent on calcium and activity dependent activation calcium dependent kinases, including the calmodulin-dependent protein kinase (CAMK). Activation of protein kinases may be achieved through other signaling pathways. It appears that sweet taste receptor signaling involves multiple activating substrates and different types and subtypes of both α-gustducin and βγ subunits of the G-protein. Although, different subtypes of sweet taste G-protein receptor subunits have been known for over a decade, their specific roles in sensing taste are not exactly clear [38, 149, 153]. For instance, Huangu et al. [149] reported the presence of β1 and γ13. The sweet taste receptor is also known to have β3 subtype subunit. For α-gustducin, Gαi-2, Gαi-3, Gα14, Gα15, Gαq, Gαs, α-transducin have been identified [38].

Mentions: It is at least 3 decades since the initial hypothesis about taste receptors was made in early 1980s by Newson and colleagues [37]. However, experimental results on the presence of these receptors showed up in the literature only after a decade following the proposal of Newson and colleagues [8, 9]. Literature data point to the extensive development of sweet taste receptor signaling in the last half-decade. This development involved not only the unraveling of some of the mechanisms of sweet taste receptor signaling but also the diversity in the localization. The discovery of sweet taste receptors in the brain is a key to better understanding of certain aspect of brain functioning. Ren et al. [24] reported the localization of sweet taste receptors in the brain and suggested that these receptors serve as glucosensor in the hypothalamus. Signaling mechanisms of sweet taste receptors in the identified tissues and cells bear some similarities. In this next section, a general model of sweet taste receptor signaling will be outlined; thereafter, the role and mechanisms of these receptors in metabolic and cognitive functions shall be discussed. The general concept of sweet taste receptor signaling is shown in Figure 1.


Sweet taste receptor signaling network: possible implication for cognitive functioning.

Welcome MO, Mastorakis NE, Pereverzev VA - Neurol Res Int (2015)

A general model of sweet taste signaling network. Sweet taste receptors possess multiple binding sites and mode of interaction for sweet molecules and they belong to class C of heterotrimeric guanine nucleotide-binding protein, G-protein [143–145]. Sweet molecules activate the G-protein by downstream signaling leading to the dissociation of the α-subunit gustducin from the βγ subunits [146, 147]. Dissociated βγ subunits of the G-protein activate phospholipase Cβ (PLCβ), leading to the formation of 1,4,5-inositol trisphosphate (IP3). IP3 is responsible for the release of Ca2+ from intracellular stores through its binding to IP3-receptor in these stores. Increase in intracellular Ca2+ activates calcium dependent kinase, monovalent selective cation channel, TRPM5 (transient receptor potential cation channel, subfamily M, member 5) [15, 44, 146], and other receptors [44, 148]. To establish the role of TRPM5 or PLCβ (type 2), Zhang et al. [4] showed that knockout of the receptor or the enzyme abolishes the sensation of taste in cells. TRPM5 may also play a role in capacitance mediated calcium entry into taste cells [147]. Modulation of purinergic signaling by taste receptor also plays useful role in taste sensation. For the initiation of purinergic release, it was recently demonstrated by Taruno et al. [148] that the voltage-gated ion channel, calcium homeostasis modulator 1 (CALHM1), is indispensable for taste-stimuli-evoked ATP release from sweet, bitter, and umami taste cells. Importantly, CALHM1 is expressed not only in sweet but also in bitter and umami taste sensing type 2 cells. Taruno et al. [148] proposed that CALHM1 is a voltage-gated ATP-release channel. Dissociated α subunit referred to as Gα-gustducin activates a phosphodiesterase (PDE) thereby decreasing intracellular cAMP levels [146, 149]. Gα-gustducin is also reported to activate adenylate cyclase (AC) to increase cAMP level [150]. According to earlier report, Clapp et al. [151] demonstrated that, compared to wild type mice, knockout of α-gustducin in the taste buds of mice resulted in high basal (unstimulated) cAMP level. The results of these authors [151] indicated that α-gustducin is necessary to maintain low level of cAMP level. Low level of cAMP is necessary to maintain the adequate signaling of Ca2+ by disinhibition of cyclic nucleotide-inhibited channels to elevate intracellular Ca2+ [38]. Changes in cAMP levels also affect other ion channels, including K+ channels. The events resulting in activation/modulation of ion channels lead to membrane depolarization and formation of action potentials. Potential-dependent release of mediators (ATP, serotonin, etc.) and peptides and calcium dependent release of peptides/biomolecules are some of the results of sweet taste receptor signaling [152]. A hallmark of sweet taste receptor signaling is the activation of transcription factors and gene expression, which might be dependent on calcium and activity dependent activation calcium dependent kinases, including the calmodulin-dependent protein kinase (CAMK). Activation of protein kinases may be achieved through other signaling pathways. It appears that sweet taste receptor signaling involves multiple activating substrates and different types and subtypes of both α-gustducin and βγ subunits of the G-protein. Although, different subtypes of sweet taste G-protein receptor subunits have been known for over a decade, their specific roles in sensing taste are not exactly clear [38, 149, 153]. For instance, Huangu et al. [149] reported the presence of β1 and γ13. The sweet taste receptor is also known to have β3 subtype subunit. For α-gustducin, Gαi-2, Gαi-3, Gα14, Gα15, Gαq, Gαs, α-transducin have been identified [38].
© Copyright Policy - open-access
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC4306214&req=5

fig1: A general model of sweet taste signaling network. Sweet taste receptors possess multiple binding sites and mode of interaction for sweet molecules and they belong to class C of heterotrimeric guanine nucleotide-binding protein, G-protein [143–145]. Sweet molecules activate the G-protein by downstream signaling leading to the dissociation of the α-subunit gustducin from the βγ subunits [146, 147]. Dissociated βγ subunits of the G-protein activate phospholipase Cβ (PLCβ), leading to the formation of 1,4,5-inositol trisphosphate (IP3). IP3 is responsible for the release of Ca2+ from intracellular stores through its binding to IP3-receptor in these stores. Increase in intracellular Ca2+ activates calcium dependent kinase, monovalent selective cation channel, TRPM5 (transient receptor potential cation channel, subfamily M, member 5) [15, 44, 146], and other receptors [44, 148]. To establish the role of TRPM5 or PLCβ (type 2), Zhang et al. [4] showed that knockout of the receptor or the enzyme abolishes the sensation of taste in cells. TRPM5 may also play a role in capacitance mediated calcium entry into taste cells [147]. Modulation of purinergic signaling by taste receptor also plays useful role in taste sensation. For the initiation of purinergic release, it was recently demonstrated by Taruno et al. [148] that the voltage-gated ion channel, calcium homeostasis modulator 1 (CALHM1), is indispensable for taste-stimuli-evoked ATP release from sweet, bitter, and umami taste cells. Importantly, CALHM1 is expressed not only in sweet but also in bitter and umami taste sensing type 2 cells. Taruno et al. [148] proposed that CALHM1 is a voltage-gated ATP-release channel. Dissociated α subunit referred to as Gα-gustducin activates a phosphodiesterase (PDE) thereby decreasing intracellular cAMP levels [146, 149]. Gα-gustducin is also reported to activate adenylate cyclase (AC) to increase cAMP level [150]. According to earlier report, Clapp et al. [151] demonstrated that, compared to wild type mice, knockout of α-gustducin in the taste buds of mice resulted in high basal (unstimulated) cAMP level. The results of these authors [151] indicated that α-gustducin is necessary to maintain low level of cAMP level. Low level of cAMP is necessary to maintain the adequate signaling of Ca2+ by disinhibition of cyclic nucleotide-inhibited channels to elevate intracellular Ca2+ [38]. Changes in cAMP levels also affect other ion channels, including K+ channels. The events resulting in activation/modulation of ion channels lead to membrane depolarization and formation of action potentials. Potential-dependent release of mediators (ATP, serotonin, etc.) and peptides and calcium dependent release of peptides/biomolecules are some of the results of sweet taste receptor signaling [152]. A hallmark of sweet taste receptor signaling is the activation of transcription factors and gene expression, which might be dependent on calcium and activity dependent activation calcium dependent kinases, including the calmodulin-dependent protein kinase (CAMK). Activation of protein kinases may be achieved through other signaling pathways. It appears that sweet taste receptor signaling involves multiple activating substrates and different types and subtypes of both α-gustducin and βγ subunits of the G-protein. Although, different subtypes of sweet taste G-protein receptor subunits have been known for over a decade, their specific roles in sensing taste are not exactly clear [38, 149, 153]. For instance, Huangu et al. [149] reported the presence of β1 and γ13. The sweet taste receptor is also known to have β3 subtype subunit. For α-gustducin, Gαi-2, Gαi-3, Gα14, Gα15, Gαq, Gαs, α-transducin have been identified [38].
Mentions: It is at least 3 decades since the initial hypothesis about taste receptors was made in early 1980s by Newson and colleagues [37]. However, experimental results on the presence of these receptors showed up in the literature only after a decade following the proposal of Newson and colleagues [8, 9]. Literature data point to the extensive development of sweet taste receptor signaling in the last half-decade. This development involved not only the unraveling of some of the mechanisms of sweet taste receptor signaling but also the diversity in the localization. The discovery of sweet taste receptors in the brain is a key to better understanding of certain aspect of brain functioning. Ren et al. [24] reported the localization of sweet taste receptors in the brain and suggested that these receptors serve as glucosensor in the hypothalamus. Signaling mechanisms of sweet taste receptors in the identified tissues and cells bear some similarities. In this next section, a general model of sweet taste receptor signaling will be outlined; thereafter, the role and mechanisms of these receptors in metabolic and cognitive functions shall be discussed. The general concept of sweet taste receptor signaling is shown in Figure 1.

Bottom Line: These receptors can sense the taste of a range of molecules and transmit the information downstream to several acceptors, modulate cell specific functions and metabolism, and mediate cell-to-cell coupling through paracrine mechanism.Recent reports indicate that sweet taste receptors are widely distributed in the body and serves specific function relative to their localization.Based on increasing evidence about the role of these receptors in the initiation and control of absorption and metabolism, and the pivotal role of metabolic (glucose) regulation in the central nervous system functioning, we propose a possible implication of sweet taste receptor signaling in modulating cognitive functioning.

View Article: PubMed Central - PubMed

Affiliation: World Scientific and Engineering Academy and Society, Ag. Ioannou Theologou 17-23, Zografou, 15773 Athens, Greece.

ABSTRACT
Sweet taste receptors are transmembrane protein network specialized in the transmission of information from special "sweet" molecules into the intracellular domain. These receptors can sense the taste of a range of molecules and transmit the information downstream to several acceptors, modulate cell specific functions and metabolism, and mediate cell-to-cell coupling through paracrine mechanism. Recent reports indicate that sweet taste receptors are widely distributed in the body and serves specific function relative to their localization. Due to their pleiotropic signaling properties and multisubstrate ligand affinity, sweet taste receptors are able to cooperatively bind multiple substances and mediate signaling by other receptors. Based on increasing evidence about the role of these receptors in the initiation and control of absorption and metabolism, and the pivotal role of metabolic (glucose) regulation in the central nervous system functioning, we propose a possible implication of sweet taste receptor signaling in modulating cognitive functioning.

No MeSH data available.


Related in: MedlinePlus