Receptor Guanylyl Cyclases in Sensory Processing

Maruyama, Ichiro

doi:10.3389/fendo.2016.00173

Cited by 24 publications

(20 citation statements)

References 143 publications

(187 reference statements)

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“…ASH activity is modulated by cGMP, and yet ASH is not known to express any guanylyl cyclases, which produce cGMP [54, 68, 69]. This suggests that other neurons may regulate its activity.…”

Section: Discussionmentioning

confidence: 99%

INX-18 and INX-19 play distinct roles in electrical synapses that modulate aversive behavior in Caenorhabditis elegans

et al. 2019

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In order to respond to changing environments and fluctuations in internal states, animals adjust their behavior through diverse neuromodulatory mechanisms. In this study we show that electrical synapses between the ASH primary quinine-detecting sensory neurons and the neighboring ASK neurons are required for modulating the aversive response to the bitter tastant quinine in C. elegans. Mutant worms that lack the electrical synapse proteins INX-18 and INX-19 become hypersensitive to dilute quinine. Cell-specific rescue experiments indicate that inx-18 operates in ASK while inx-19 is required in both ASK and ASH for proper quinine sensitivity. Imaging analyses find that INX-19 in ASK and ASH localizes to the same regions in the nerve ring, suggesting that both sides of ASK-ASH electrical synapses contain INX-19. While inx-18 and inx-19 mutant animals have a similar behavioral phenotype, several lines of evidence suggest the proteins encoded by these genes play different roles in modulating the aversive quinine response. First, INX-18 and INX-19 localize to different regions of the nerve ring, indicating that they are not present in the same synapses. Second, removing inx-18 disrupts the distribution of INX-19, while removing inx-19 does not alter INX-18 localization. Finally, by using a fluorescent cGMP reporter, we find that INX-18 and INX-19 have distinct roles in establishing cGMP levels in ASK and ASH. Together, these results demonstrate that electrical synapses containing INX-18 and INX-19 facilitate modulation of ASH nociceptive signaling. Our findings support the idea that a network of electrical synapses mediates cGMP exchange between neurons, enabling modulation of sensory responses and behavior.

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“…ASH activity is modulated by cGMP, and yet ASH is not known to express any guanylyl cyclases, which produce cGMP [54, 68, 69]. This suggests that other neurons may regulate its activity.…”

Section: Discussionmentioning

confidence: 99%

INX-18 and INX-19 play distinct roles in electrical synapses that modulate aversive behavior in Caenorhabditis elegans

et al. 2019

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“…Indeed, crystal structures of the intracellular domain show that the kinase domain dimer adopts a symmetric, back-to-back, inactive structure stabilized by the AP-2 helices (Figure 2(a)) [63]. Ligand binding to the extracellular domain of the EGFR dimer induces ~140 o rotation of the transmembrane domain, parallel to the plane of the cell membrane [37], as observed in many other cell-surface receptors [36, 85,86]. This rotation of the transmembrane domain is supported by an NMR structural study showing that the transmembrane domain of EGFR has two surfaces through which the domains interact with each other [87].…”

Section: Mechanism Of Activation Of Egfr Dimers By Ligand Binding: Thmentioning

confidence: 99%

Activation of the EGF Receptor by Ligand Binding and Oncogenic Mutations: The “Rotation Model”

Purba

Saita

Maruyama

2017

Preprint

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Abstract:The epidermal growth factor receptor (EGFR) plays vital roles in cellular processes including cell proliferation, survival, motility and differentiation. Dysregulated activation of the receptor is often implicated in human cancers. EGFR is synthesized as a single-pass transmembrane protein, which consists of an extracellular ligand-binding domain and an intracellular kinase domain separated by a single transmembrane domain. The receptor is activated by a variety of polypeptide ligands such as epidermal growth factor and transforming growth factor α. It has long been thought that EGFR is activated by ligand-induced dimerization of the receptor monomer, which brings intracellular kinase domains into close proximity for trans-autophosphorylation. An increasing number of diverse studies, however, demonstrate that EGFR is present as a pre-formed, yet inactive, dimer prior to ligand binding. Furthermore, recent progress in structural studies has provided insight into conformational changes during the activation of a preformed EGFR dimer. Upon ligand binding to the extracellular domain of EGFR, its transmembrane domains rotate or twist parallel to the plane of the cell membrane, resulting in reorientation of the intracellular kinase domain dimer from a symmetric inactive configuration to an asymmetric active form (the "rotation model"). This model is also able to explain how oncogenic mutations activate the receptor in the absence of ligand without assuming that the mutations induce receptor dimerization. In this review, we discuss mechanisms underlying ligand-induced activation of the preformed EGFR dimer, as well as how oncogenic mutations constitutively activate the receptor dimer, based on the rotation model.Keywords: cancer; cell-surface receptor; EGFR; molecular mechanism; phosphorylation; receptor tyrosine kinase; transmembrane signal transduction Peer-reviewed version available at Cells 2017, 6, , 13; doi:10.3390/cells60200132 of 24 IntroductionThe epidermal growth factor receptor (EGFR) is a member of the ErbB receptor family, which is a member of the receptor tyrosine kinase superfamily. The ErbB receptor family consists of EGFR (also known as ErbB1 or HER1), ErbB2 (Neu or HER2), ErbB3 (HER3) and ErbB4 (HER4). EGFR is involved in a variety of cellular processes including cell proliferation, motility, survival and differentiation, and is essential for normal animal development [1][2][3][4]. Aberrant activation of EGFR is implicated in a variety of human cancers [5]. The receptor is activated by binding of various ligands including epidermal growth factor (EGF), transforming growth factor α (TGFα), amphiregulin (AREG), epigen, β-cellulin, heparin-binding EGF (HB-EGF) and epiregulin [6,7]. EGFR is a singlepass transmembrane protein, consisting of an extracellular domain, a transmembrane domain, a juxtamembrane (JM) segment, a kinase domain, and a C-terminal regulatory tail ( Figure 1) [8,9]. Upon ligand binding, the C-terminal tail becomes tyrosinephosphorylated, and mediates interactions between the re...

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“…cGMP-producing guanylyl cyclases (GCs) also comprise membrane-bound (type 1) and soluble (type 2) forms [ 13 ]. Single membrane-spanning GCs, named particulate GCs (pGCs), exist in animals and participate in sensory processing [ 14 , 15 ]. For example, pGC-G was proved to be a thermosensory protein [ 16 ].…”

Section: Introduction To Cyclic Nucleotides and Signal Transductiomentioning

confidence: 99%

Advances, Perspectives and Potential Engineering Strategies of Light-Gated Phosphodiesterases for Optogenetic Applications

Tian

Yang

Gao

2020

IJMS

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The second messengers, cyclic adenosine 3′-5′-monophosphate (cAMP) and cyclic guanosine 3′-5′-monophosphate (cGMP), play important roles in many animal cells by regulating intracellular signaling pathways and modulating cell physiology. Environmental cues like temperature, light, and chemical compounds can stimulate cell surface receptors and trigger the generation of second messengers and the following regulations. The spread of cAMP and cGMP is further shaped by cyclic nucleotide phosphodiesterases (PDEs) for orchestration of intracellular microdomain signaling. However, localized intracellular cAMP and cGMP signaling requires further investigation. Optogenetic manipulation of cAMP and cGMP offers new opportunities for spatio-temporally precise study of their signaling mechanism. Light-gated nucleotide cyclases are well developed and applied for cAMP/cGMP manipulation. Recently discovered rhodopsin phosphodiesterase genes from protists established a new and direct biological connection between light and PDEs. Light-regulated PDEs are under development, and of demand to complete the toolkit for cAMP/cGMP manipulation. In this review, we summarize the state of the art, pros and cons of artificial and natural light-regulated PDEs, and discuss potential new strategies of developing light-gated PDEs for optogenetic manipulation.

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Receptor Guanylyl Cyclases in Sensory Processing

Cited by 24 publications

References 143 publications

INX-18 and INX-19 play distinct roles in electrical synapses that modulate aversive behavior in Caenorhabditis elegans

INX-18 and INX-19 play distinct roles in electrical synapses that modulate aversive behavior in Caenorhabditis elegans

Activation of the EGF Receptor by Ligand Binding and Oncogenic Mutations: The “Rotation Model”

Advances, Perspectives and Potential Engineering Strategies of Light-Gated Phosphodiesterases for Optogenetic Applications

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Receptor Guanylyl Cyclases in Sensory Processing

Cited by 24 publications

References 143 publications

INX-18 and INX-19 play distinct roles in electrical synapses that modulate aversive behavior in Caenorhabditis elegans

INX-18 and INX-19 play distinct roles in electrical synapses that modulate aversive behavior in Caenorhabditis elegans

Activation of the EGF Receptor by Ligand Binding and Oncogenic Mutations: The &ldquo;Rotation Model&rdquo;

Advances, Perspectives and Potential Engineering Strategies of Light-Gated Phosphodiesterases for Optogenetic Applications

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Activation of the EGF Receptor by Ligand Binding and Oncogenic Mutations: The “Rotation Model”