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  1. Artikel ; Online: Chemosensory receptor specificity and regulation.

    Dalton, Ryan P / Lomvardas, Stavros

    Annual review of neuroscience

    2015  Band 38, Seite(n) 331–349

    Abstract: The senses provide a means by which data on the physical and chemical properties of the environment may be collected and meaningfully interpreted. Sensation begins at the periphery, where a multitude of different sensory cell types are activated by ... ...

    Abstract The senses provide a means by which data on the physical and chemical properties of the environment may be collected and meaningfully interpreted. Sensation begins at the periphery, where a multitude of different sensory cell types are activated by environmental stimuli as different as photons and odorant molecules. Stimulus sensitivity is due to expression of different cell surface sensory receptors, and therefore the receptive field of each sense is defined by the aggregate of expressed receptors in each sensory tissue. Here, we review current understanding on patterns of expression and modes of regulation of sensory receptors.
    Mesh-Begriff(e) Animals ; Receptors, G-Protein-Coupled/genetics ; Receptors, G-Protein-Coupled/physiology ; Receptors, Odorant/genetics ; Receptors, Odorant/physiology ; Sensory Receptor Cells/physiology ; Vomeronasal Organ/physiology
    Chemische Substanzen Receptors, G-Protein-Coupled ; Receptors, Odorant ; taste receptors, type 1 ; taste receptors, type 2
    Sprache Englisch
    Erscheinungsdatum 2015-07-08
    Erscheinungsland United States
    Dokumenttyp Journal Article ; Research Support, N.I.H., Extramural ; Review
    ZDB-ID 282459-0
    ISSN 1545-4126 ; 0147-006X
    ISSN (online) 1545-4126
    ISSN 0147-006X
    DOI 10.1146/annurev-neuro-071714-034145
    Datenquelle MEDical Literature Analysis and Retrieval System OnLINE

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  2. Artikel: ER stress transforms random olfactory receptor choice into axon targeting precision

    Shayya, Hani J. / Kahiapo, Jerome K. / Duffié, Rachel / Lehmann, Katherine S. / Bashkirova, Lisa / Monahan, Kevin / Dalton, Ryan P. / Gao, Joanna / Jiao, Song / Schieren, Ira / Belluscio, Leonardo / Lomvardas, Stavros

    Cell. 2022 Aug. 25,

    2022  

    Abstract: Olfactory sensory neurons (OSNs) convert the stochastic choice of one of >1,000 olfactory receptor (OR) genes into precise and stereotyped axon targeting of OR-specific glomeruli in the olfactory bulb. Here, we show that the PERK arm of the unfolded ... ...

    Abstract Olfactory sensory neurons (OSNs) convert the stochastic choice of one of >1,000 olfactory receptor (OR) genes into precise and stereotyped axon targeting of OR-specific glomeruli in the olfactory bulb. Here, we show that the PERK arm of the unfolded protein response (UPR) regulates both the glomerular coalescence of like axons and the specificity of their projections. Subtle differences in OR protein sequences lead to distinct patterns of endoplasmic reticulum (ER) stress during OSN development, converting OR identity into distinct gene expression signatures. We identify the transcription factor Ddit3 as a key effector of PERK signaling that maps OR-dependent ER stress patterns to the transcriptional regulation of axon guidance and cell-adhesion genes, instructing targeting precision. Our results extend the known functions of the UPR from a quality-control pathway that protects cells from misfolded proteins to a sensor of cellular identity that interprets physiological states to direct axon wiring.
    Schlagwörter axons ; cell adhesion ; endoplasmic reticulum ; gene expression ; olfactory bulb ; olfactory receptors ; quality control ; transcription (genetics) ; transcription factors ; unfolded protein response
    Sprache Englisch
    Erscheinungsverlauf 2022-0825
    Erscheinungsort Elsevier Inc.
    Dokumenttyp Artikel
    Anmerkung Pre-press version
    ZDB-ID 187009-9
    ISSN 1097-4172 ; 0092-8674
    ISSN (online) 1097-4172
    ISSN 0092-8674
    DOI 10.1016/j.cell.2022.08.025
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  3. Artikel ; Online: ER stress transforms random olfactory receptor choice into axon targeting precision.

    Shayya, Hani J / Kahiapo, Jerome K / Duffié, Rachel / Lehmann, Katherine S / Bashkirova, Lisa / Monahan, Kevin / Dalton, Ryan P / Gao, Joanna / Jiao, Song / Schieren, Ira / Belluscio, Leonardo / Lomvardas, Stavros

    Cell

    2022  Band 185, Heft 21, Seite(n) 3896–3912.e22

    Abstract: Olfactory sensory neurons (OSNs) convert the stochastic choice of one of >1,000 olfactory receptor (OR) genes into precise and stereotyped axon targeting of OR-specific glomeruli in the olfactory bulb. Here, we show that the PERK arm of the unfolded ... ...

    Abstract Olfactory sensory neurons (OSNs) convert the stochastic choice of one of >1,000 olfactory receptor (OR) genes into precise and stereotyped axon targeting of OR-specific glomeruli in the olfactory bulb. Here, we show that the PERK arm of the unfolded protein response (UPR) regulates both the glomerular coalescence of like axons and the specificity of their projections. Subtle differences in OR protein sequences lead to distinct patterns of endoplasmic reticulum (ER) stress during OSN development, converting OR identity into distinct gene expression signatures. We identify the transcription factor Ddit3 as a key effector of PERK signaling that maps OR-dependent ER stress patterns to the transcriptional regulation of axon guidance and cell-adhesion genes, instructing targeting precision. Our results extend the known functions of the UPR from a quality-control pathway that protects cells from misfolded proteins to a sensor of cellular identity that interprets physiological states to direct axon wiring.
    Mesh-Begriff(e) Animals ; Axons/metabolism ; Endoplasmic Reticulum Stress ; Mice ; Olfactory Bulb ; Olfactory Receptor Neurons/metabolism ; Receptors, Odorant/genetics ; Receptors, Odorant/metabolism ; Transcription Factors/metabolism
    Chemische Substanzen Receptors, Odorant ; Transcription Factors
    Sprache Englisch
    Erscheinungsdatum 2022-09-26
    Erscheinungsland United States
    Dokumenttyp Journal Article ; Research Support, N.I.H., Extramural
    ZDB-ID 187009-9
    ISSN 1097-4172 ; 0092-8674
    ISSN (online) 1097-4172
    ISSN 0092-8674
    DOI 10.1016/j.cell.2022.08.025
    Datenquelle MEDical Literature Analysis and Retrieval System OnLINE

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  4. Artikel ; Online: Co-opting the unfolded protein response to elicit olfactory receptor feedback.

    Dalton, Ryan P / Lyons, David B / Lomvardas, Stavros

    Cell

    2013  Band 155, Heft 2, Seite(n) 321–332

    Abstract: Olfactory receptor (OR) expression requires the transcriptional activation of 1 out of 1,000s of OR alleles and a feedback signal that preserves this transcriptional choice. The mechanism by which olfactory sensory neurons (OSNs) detect ORs to signal to ... ...

    Abstract Olfactory receptor (OR) expression requires the transcriptional activation of 1 out of 1,000s of OR alleles and a feedback signal that preserves this transcriptional choice. The mechanism by which olfactory sensory neurons (OSNs) detect ORs to signal to the nucleus remains elusive. Here, we show that OR proteins generate this feedback by activating the unfolded protein response (UPR). OR expression induces Perk-mediated phosphorylation of the translation initiation factor eif2α causing selective translation of activating transcription factor 5 (ATF5). ATF5 induces the transcription of adenylyl cyclase 3 (Adcy3), which relieves the UPR. Our data provide a role for the UPR in defining neuronal identity and cell fate commitment and support a two-step model for the feedback signal: (1) OR protein, as a stress stimulus, alters the translational landscape of the OSN and induces Adcy3 expression; (2), Adcy3 relieves that stress, restores global translation, and makes OR choice permanent.
    Mesh-Begriff(e) Activating Transcription Factors/genetics ; Activating Transcription Factors/metabolism ; Adenylyl Cyclases/metabolism ; Animals ; Endoplasmic Reticulum/metabolism ; Eukaryotic Initiation Factor-2/metabolism ; Feedback, Physiological ; Mice ; Mice, Knockout ; Neurons/cytology ; Neurons/metabolism ; Olfactory Receptor Neurons/metabolism ; Receptors, Odorant/genetics ; Receptors, Odorant/metabolism ; Unfolded Protein Response ; eIF-2 Kinase/metabolism
    Chemische Substanzen Activating Transcription Factors ; Atf5 protein, mouse ; Eukaryotic Initiation Factor-2 ; Receptors, Odorant ; PERK kinase (EC 2.7.11.1) ; eIF-2 Kinase (EC 2.7.11.1) ; Adenylyl Cyclases (EC 4.6.1.1) ; adenylate cyclase 3 (EC 4.6.1.1)
    Sprache Englisch
    Erscheinungsdatum 2013-10-11
    Erscheinungsland United States
    Dokumenttyp Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 187009-9
    ISSN 1097-4172 ; 0092-8674
    ISSN (online) 1097-4172
    ISSN 0092-8674
    DOI 10.1016/j.cell.2013.09.033
    Datenquelle MEDical Literature Analysis and Retrieval System OnLINE

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  5. Artikel: Affinity purification of microRNA-133a with the cardiac transcription factor, Hand2

    Vo, Ngan K / Dalton, Ryan P / Liu, Ning / Olson, Eric N / Goodman, Richard H

    Proceedings of the National Academy of Sciences of the United States of America. 2010 Nov. 9, v. 107, no. 45

    2010  

    Abstract: Predictions of microRNA-mRNA interactions typically rely on bioinformatic algorithms, but these algorithms only suggest the possibility of microRNA binding and may miss important interactions as well as falsely predict others. We developed an affinity ... ...

    Abstract Predictions of microRNA-mRNA interactions typically rely on bioinformatic algorithms, but these algorithms only suggest the possibility of microRNA binding and may miss important interactions as well as falsely predict others. We developed an affinity purification approach to empirically identify microRNAs associated with the 3'UTR of the mRNA encoding Hand2, a transcription factor essential for cardiac development. In addition to miR-1, a known regulator of Hand2 expression, we determined that the Hand2 3'UTR also associated with miR-133a, a microRNA cotranscribed with miR-1 in cardiac and muscle cells. Using a sequential binding assay, we showed that miR-1 and miR-133a could occupy the Hand2 3'UTR concurrently. miR-133a inhibited Hand2 expression in tissue culture models, and miR-133a double knockout mice had elevated levels of Hand2 mRNA and protein. We conclude that Hand2 is regulated by miR-133a in addition to miR-1. The affinity purification assay should be generally applicable for identifying other microRNA-mRNA interactions.
    Schlagwörter 3' untranslated regions ; algorithms ; bioinformatics ; cardiomyocytes ; knockout mutants ; microRNA ; models ; prediction ; tissue culture ; transcription factors
    Sprache Englisch
    Erscheinungsverlauf 2010-1109
    Umfang p. 19231-19236.
    Erscheinungsort National Academy of Sciences
    Dokumenttyp Artikel
    ZDB-ID 209104-5
    ISSN 1091-6490 ; 0027-8424
    ISSN (online) 1091-6490
    ISSN 0027-8424
    DOI 10.1073/pnas.1013162107
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  6. Artikel ; Online: Affinity purification of microRNA-133a with the cardiac transcription factor, Hand2.

    Vo, Ngan K / Dalton, Ryan P / Liu, Ning / Olson, Eric N / Goodman, Richard H

    Proceedings of the National Academy of Sciences of the United States of America

    2010  Band 107, Heft 45, Seite(n) 19231–19236

    Abstract: Predictions of microRNA-mRNA interactions typically rely on bioinformatic algorithms, but these algorithms only suggest the possibility of microRNA binding and may miss important interactions as well as falsely predict others. We developed an affinity ... ...

    Abstract Predictions of microRNA-mRNA interactions typically rely on bioinformatic algorithms, but these algorithms only suggest the possibility of microRNA binding and may miss important interactions as well as falsely predict others. We developed an affinity purification approach to empirically identify microRNAs associated with the 3'UTR of the mRNA encoding Hand2, a transcription factor essential for cardiac development. In addition to miR-1, a known regulator of Hand2 expression, we determined that the Hand2 3'UTR also associated with miR-133a, a microRNA cotranscribed with miR-1 in cardiac and muscle cells. Using a sequential binding assay, we showed that miR-1 and miR-133a could occupy the Hand2 3'UTR concurrently. miR-133a inhibited Hand2 expression in tissue culture models, and miR-133a double knockout mice had elevated levels of Hand2 mRNA and protein. We conclude that Hand2 is regulated by miR-133a in addition to miR-1. The affinity purification assay should be generally applicable for identifying other microRNA-mRNA interactions.
    Mesh-Begriff(e) 3' Untranslated Regions ; Animals ; Basic Helix-Loop-Helix Transcription Factors/genetics ; Basic Helix-Loop-Helix Transcription Factors/isolation & purification ; Basic Helix-Loop-Helix Transcription Factors/metabolism ; Binding Sites ; Heart ; Humans ; Mice ; Mice, Knockout ; MicroRNAs/isolation & purification ; MicroRNAs/metabolism ; Myocardium/metabolism ; RNA, Messenger/analysis ; RNA, Messenger/metabolism ; Rats
    Chemische Substanzen 3' Untranslated Regions ; Basic Helix-Loop-Helix Transcription Factors ; Hand2 protein, mouse ; MicroRNAs ; Mirn133 microRNA, mouse ; RNA, Messenger
    Sprache Englisch
    Erscheinungsdatum 2010-10-25
    Erscheinungsland United States
    Dokumenttyp Journal Article ; Research Support, N.I.H., Extramural
    ZDB-ID 209104-5
    ISSN 1091-6490 ; 0027-8424
    ISSN (online) 1091-6490
    ISSN 0027-8424
    DOI 10.1073/pnas.1013162107
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  7. Artikel: Co-Opting the Unfolded Protein Response to Elicit Olfactory Receptor Feedback

    Dalton, Ryan P. / Lyons, David B. / Lomvardas, Stavros

    Cell

    Band v. 155,, Heft no. 2

    Abstract: Olfactory receptor (OR) expression requires the transcriptional activation of 1 out of 1,000s of OR alleles and a feedback signal that preserves this transcriptional choice. The mechanism by which olfactory sensory neurons (OSNs) detect ORs to signal to ... ...

    Abstract Olfactory receptor (OR) expression requires the transcriptional activation of 1 out of 1,000s of OR alleles and a feedback signal that preserves this transcriptional choice. The mechanism by which olfactory sensory neurons (OSNs) detect ORs to signal to the nucleus remains elusive. Here, we show that OR proteins generate this feedback by activating the unfolded protein response (UPR). OR expression induces Perk-mediated phosphorylation of the translation initiation factor eif2α causing selective translation of activating transcription factor 5 (ATF5). ATF5 induces the transcription of adenylyl cyclase 3 (Adcy3), which relieves the UPR. Our data provide a role for the UPR in defining neuronal identity and cell fate commitment and support a two-step model for the feedback signal: (1) OR protein, as a stress stimulus, alters the translational landscape of the OSN and induces Adcy3 expression; (2), Adcy3 relieves that stress, restores global translation, and makes OR choice permanent.
    Schlagwörter adenylate cyclase ; unfolded protein response ; alleles ; sensory neurons ; transcription factors ; transcription (genetics) ; transcriptional activation ; translation (genetics) ; models ; olfactory receptors ; proteins ; phosphorylation
    Sprache Englisch
    Dokumenttyp Artikel
    ISSN 0092-8674
    Datenquelle AGRIS - International Information System for the Agricultural Sciences and Technology

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  8. Artikel: Affinity purification of microRNA-133a with the cardiac transcription factor, Hand2

    Vo, Ngan K. / Dalton, Ryan P. / Liu, Ning / Olson, Eric N. / Goodman, Richard H.
    Sprache Englisch
    Dokumenttyp Artikel
    Datenquelle AGRIS - International Information System for the Agricultural Sciences and Technology

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