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  1. Book: From molecules to networks

    Byrne, John H. / Heidelberger, Ruth / Waxham, M. Neal

    an introduction to cellular and molecular neuroscience

    2014  

    Author's details John H. Byrne ; Ruth Heidelberger ; M. Neal Waxham
    Keywords Nervous System / cytology ; Nerve Net ; Neurobiology / methods ; Neurons ; Cytology ; Molecular neurobiology
    Subject code 612.8
    Language English
    Size XVI, 675 S. : Ill., graph. Darst., 28cm
    Edition 3. ed.
    Publisher Elsevier Acad. Press
    Publishing place Amsterdam u.a.
    Publishing country Netherlands
    Document type Book
    HBZ-ID HT018401811
    ISBN 978-0-12-397179-1 ; 0-12-397179-9
    Database Catalogue ZB MED Medicine, Health

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    Shelf markLoan statusLocation
    2014 A 3655 available for loan (reading room) Lesesaal EG

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  2. Article ; Online: Syntaxin 3 is haplosufficient for long-term photoreceptor survival in the mouse retina.

    Perez-Hurtado, Mariajose / Dao, Calvin / Saenz, Amanda E / Heidelberger, Ruth

    Frontiers in ophthalmology

    2023  Volume 3

    Abstract: Biallelic loss-of-function mutations in the syntaxin 3 gene have been linked to a severe retinal dystrophy in humans that presents in early childhood. In mouse models, biallelic inactivation of the syntaxin 3 gene in photoreceptors rapidly leads to their ...

    Abstract Biallelic loss-of-function mutations in the syntaxin 3 gene have been linked to a severe retinal dystrophy in humans that presents in early childhood. In mouse models, biallelic inactivation of the syntaxin 3 gene in photoreceptors rapidly leads to their death. What is not known is whether a monoallelic syntaxin 3 loss-of-function mutation might cause photoreceptor loss with advancing age. To address this question, we compared the outer nuclear layer of older adult mice (≈ 20 months of age) that were heterozygous for syntaxin 3 with those of similarly-aged control mice. We found that the photoreceptor layer maintains its thickness in mice that are heterozygous for syntaxin 3 relative to controls and that photoreceptor somatic counts are comparable. In addition, dendritic sprouting of the rod bipolar cell dendrites into the outer nuclear layer, which occurs following the loss of functional rod targets, was similar between genotypes. Thus, syntaxin 3 appears to be haplosufficient for photoreceptor survival, even with advancing age.
    Language English
    Publishing date 2023-06-14
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 3123828-2
    ISSN 2674-0826 ; 2674-0826
    ISSN (online) 2674-0826
    ISSN 2674-0826
    DOI 10.3389/fopht.2023.1208805
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: Syntaxin 3 is haplosufficient for long-term photoreceptor survival in the mouse retina

    Mariajose Perez-Hurtado / Calvin Dao / Amanda E. Saenz / Ruth Heidelberger

    Frontiers in Ophthalmology, Vol

    2023  Volume 3

    Abstract: Biallelic loss-of-function mutations in the syntaxin 3 gene have been linked to a severe retinal dystrophy in humans that presents in early childhood. In mouse models, biallelic inactivation of the syntaxin 3 gene in photoreceptors rapidly leads to their ...

    Abstract Biallelic loss-of-function mutations in the syntaxin 3 gene have been linked to a severe retinal dystrophy in humans that presents in early childhood. In mouse models, biallelic inactivation of the syntaxin 3 gene in photoreceptors rapidly leads to their death. What is not known is whether a monoallelic syntaxin 3 loss-of-function mutation might cause photoreceptor loss with advancing age. To address this question, we compared the outer nuclear layer of older adult mice (≈ 20 months of age) that were heterozygous for syntaxin 3 with those of similarly-aged control mice. We found that the photoreceptor layer maintains its thickness in mice that are heterozygous for syntaxin 3 relative to controls and that photoreceptor somatic counts are comparable. In addition, dendritic sprouting of the rod bipolar cell dendrites into the outer nuclear layer, which occurs following the loss of functional rod targets, was similar between genotypes. Thus, syntaxin 3 appears to be haplosufficient for photoreceptor survival, even with advancing age.
    Keywords STX3 ; syntaxin 3B ; SNAREopathy ; retinal degeneration ; retinal dystrophy ; EOSRD ; Medicine ; R
    Subject code 570
    Language English
    Publishing date 2023-06-01T00:00:00Z
    Publisher Frontiers Media S.A.
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  4. Article ; Online: Regulation of Syntaxin3B-Mediated Membrane Fusion by T14, Munc18, and Complexin.

    Nishad, Rajkishor / Betancourt-Solis, Miguel / Dey, Himani / Heidelberger, Ruth / McNew, James A

    Biomolecules

    2023  Volume 13, Issue 10

    Abstract: Retinal neurons that form ribbon-style synapses operate over a wide dynamic range, continuously relaying visual information to their downstream targets. The remarkable signaling abilities of these neurons are supported by specialized presynaptic ... ...

    Abstract Retinal neurons that form ribbon-style synapses operate over a wide dynamic range, continuously relaying visual information to their downstream targets. The remarkable signaling abilities of these neurons are supported by specialized presynaptic machinery, one component of which is syntaxin3B. Syntaxin3B is an essential t-SNARE protein of photoreceptors and bipolar cells that is required for neurotransmitter release. It has a light-regulated phosphorylation site in its N-terminal domain at T14 that has been proposed to modulate membrane fusion. However, a direct test of the latter has been lacking. Using a well-controlled in vitro fusion assay, we found that a phosphomimetic T14 syntaxin3B mutation leads to a small but significant enhancement of SNARE-mediated membrane fusion following the formation of the t-SNARE complex. While the addition of Munc18a had only a minimal effect on membrane fusion mediated by SNARE complexes containing wild-type syntaxin3B, a more significant enhancement was observed in the presence of Munc18a when the SNARE complexes contained a syntaxin3B T14 phosphomimetic mutant. Finally, we showed that the retinal-specific complexins (Cpx III and Cpx IV) inhibited membrane fusion mediated by syntaxin3B-containing SNARE complexes in a dose-dependent manner. Collectively, our results establish that membrane fusion mediated by syntaxin3B-containing SNARE complexes is regulated by the T14 residue of syntaxin3B, Munc18a, and Cpxs III and IV.
    MeSH term(s) Membrane Fusion/physiology ; Synapses/metabolism ; Synaptic Transmission/genetics ; Retina/metabolism ; SNARE Proteins/genetics ; SNARE Proteins/metabolism ; Protein Binding
    Chemical Substances SNARE Proteins
    Language English
    Publishing date 2023-09-28
    Publishing country Switzerland
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 2701262-1
    ISSN 2218-273X ; 2218-273X
    ISSN (online) 2218-273X
    ISSN 2218-273X
    DOI 10.3390/biom13101463
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article ; Online: Neuroscience: sensors and synchronicity.

    Heidelberger, Ruth

    Nature

    2007  Volume 450, Issue 7170, Page(s) 623–625

    MeSH term(s) Action Potentials/drug effects ; Animals ; Calcium/metabolism ; Calcium/pharmacology ; Mice ; Neurotransmitter Agents/secretion ; Presynaptic Terminals/drug effects ; Presynaptic Terminals/secretion ; Synapses/drug effects ; Synapses/secretion ; Synaptic Transmission/drug effects ; Synaptotagmin II/deficiency ; Synaptotagmin II/genetics ; Synaptotagmin II/metabolism
    Chemical Substances Neurotransmitter Agents ; Synaptotagmin II ; Calcium (SY7Q814VUP)
    Language English
    Publishing date 2007-11-29
    Publishing country England
    Document type Comment ; News
    ZDB-ID 120714-3
    ISSN 1476-4687 ; 0028-0836
    ISSN (online) 1476-4687
    ISSN 0028-0836
    DOI 10.1038/450623a
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  6. Article: Mechanisms of tonic, graded release: lessons from the vertebrate photoreceptor.

    Heidelberger, Ruth

    The Journal of physiology

    2007  Volume 585, Issue Pt 3, Page(s) 663–667

    Abstract: The release of neurotransmitter via exocytosis is a highly conserved, fundamental feature of nervous system function. At conventional synapses, neurotransmitter release occurs as a brief burst of exocytosis triggered by an action potential. By contrast, ... ...

    Abstract The release of neurotransmitter via exocytosis is a highly conserved, fundamental feature of nervous system function. At conventional synapses, neurotransmitter release occurs as a brief burst of exocytosis triggered by an action potential. By contrast, at the first synapse of the vertebrate visual pathway, not only is the calcium-dependent release of neurotransmitter typically graded with respect to the presynaptic membrane potential, but release can be maintained throughout the duration of a sustained stimulus. The specializations that provide for graded and sustained release are not well-defined. However, recent advances in our understanding of basic synaptic vesicle dynamics and the calcium sensitivity of the release process at these and other central, glutamatergic neurons have shed some light on the photoreceptor's extraordinary abilities.
    MeSH term(s) Animals ; Exocytosis/physiology ; Humans ; Neurotransmitter Agents/metabolism ; Photoreceptor Cells, Vertebrate/metabolism ; Photoreceptor Cells, Vertebrate/physiology
    Chemical Substances Neurotransmitter Agents
    Language English
    Publishing date 2007-12-15
    Publishing country England
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Review
    ZDB-ID 3115-x
    ISSN 1469-7793 ; 0022-3751
    ISSN (online) 1469-7793
    ISSN 0022-3751
    DOI 10.1113/jphysiol.2007.137927
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  7. Article ; Online: Calmodulin Binding to Connexin 35: Specializations to Function as an Electrical Synapse.

    Aseervatham, Jaya / Li, Xiaofan / Mitchell, Cheryl K / Lin, Ya-Ping / Heidelberger, Ruth / O'Brien, John

    International journal of molecular sciences

    2020  Volume 21, Issue 17

    Abstract: Calmodulin binding is a nearly universal property of gap junction proteins, imparting a calcium-dependent uncoupling behavior that can serve in an emergency to decouple a stressed cell from its neighbors. However, gap junctions that function as ... ...

    Abstract Calmodulin binding is a nearly universal property of gap junction proteins, imparting a calcium-dependent uncoupling behavior that can serve in an emergency to decouple a stressed cell from its neighbors. However, gap junctions that function as electrical synapses within networks of neurons routinely encounter large fluctuations in local cytoplasmic calcium concentration; frequent uncoupling would be impractical and counterproductive. We have studied the properties and functional consequences of calmodulin binding to the electrical synapse protein Connexin 35 (Cx35 or gjd2b), homologous to mammalian Connexin 36 (Cx36 or gjd2). We find that specializations in Cx35 calmodulin binding sites make it relatively impervious to moderately high levels of cytoplasmic calcium. Calmodulin binding to a site in the C-terminus causes uncoupling when calcium reaches low micromolar concentrations, a behavior prevented by mutations that eliminate calmodulin binding. However, milder stimuli promote calcium/calmodulin-dependent protein kinase II activity that potentiates coupling without interference from calmodulin binding. A second calmodulin binding site in the end of the Cx35 cytoplasmic loop, homologous to a calmodulin binding site present in many connexins, binds calmodulin with very low affinity and stoichiometry. Together, the calmodulin binding sites cause Cx35 to uncouple only at extreme levels of intracellular calcium.
    MeSH term(s) Calcium Signaling ; Calcium-Calmodulin-Dependent Protein Kinase Type 2/metabolism ; Calmodulin/genetics ; Calmodulin/metabolism ; Connexins/genetics ; Connexins/metabolism ; Electrical Synapses/physiology ; Gap Junctions/physiology ; HeLa Cells ; Humans ; Mutation ; Phosphorylation ; Protein Binding ; Protein Transport ; Gap Junction delta-2 Protein
    Chemical Substances Calmodulin ; Connexins ; Calcium-Calmodulin-Dependent Protein Kinase Type 2 (EC 2.7.11.17)
    Language English
    Publishing date 2020-09-01
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2019364-6
    ISSN 1422-0067 ; 1422-0067 ; 1661-6596
    ISSN (online) 1422-0067
    ISSN 1422-0067 ; 1661-6596
    DOI 10.3390/ijms21176346
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  8. Article ; Online: Simultaneous Release of Multiple Vesicles from Rods Involves Synaptic Ribbons and Syntaxin 3B.

    Hays, Cassandra L / Grassmeyer, Justin J / Wen, Xiangyi / Janz, Roger / Heidelberger, Ruth / Thoreson, Wallace B

    Biophysical journal

    2019  Volume 118, Issue 4, Page(s) 967–979

    Abstract: First proposed as a specialized mode of release at sensory neurons possessing ribbon synapses, multivesicular release has since been described throughout the central nervous system. Many aspects of multivesicular release remain poorly understood. We ... ...

    Abstract First proposed as a specialized mode of release at sensory neurons possessing ribbon synapses, multivesicular release has since been described throughout the central nervous system. Many aspects of multivesicular release remain poorly understood. We explored mechanisms underlying simultaneous multivesicular release at ribbon synapses in salamander retinal rod photoreceptors. We assessed spontaneous release presynaptically by recording glutamate transporter anion currents (I
    MeSH term(s) Excitatory Postsynaptic Potentials ; Qa-SNARE Proteins ; Retinal Rod Photoreceptor Cells ; Synapses ; Synaptic Transmission ; Synaptic Vesicles
    Chemical Substances Qa-SNARE Proteins
    Language English
    Publishing date 2019-10-10
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 218078-9
    ISSN 1542-0086 ; 0006-3495
    ISSN (online) 1542-0086
    ISSN 0006-3495
    DOI 10.1016/j.bpj.2019.10.006
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  9. Article: Phosphorylation of the Retinal Ribbon Synapse Specific t-SNARE Protein Syntaxin3B Is Regulated by Light via a Ca

    Campbell, Joseph R / Li, Hongyan / Wang, Yanzhao / Kozhemyakin, Maxim / Hunt, Albert J / Liu, Xiaoqin / Janz, Roger / Heidelberger, Ruth

    Frontiers in cellular neuroscience

    2020  Volume 14, Page(s) 587072

    Abstract: Neurotransmitter release at retinal ribbon-style synapses utilizes a specialized t-SNARE protein called syntaxin3B (STX3B). In contrast to other syntaxins, STX3 proteins can be ... ...

    Abstract Neurotransmitter release at retinal ribbon-style synapses utilizes a specialized t-SNARE protein called syntaxin3B (STX3B). In contrast to other syntaxins, STX3 proteins can be phosphorylated
    Language English
    Publishing date 2020-10-20
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2452963-1
    ISSN 1662-5102
    ISSN 1662-5102
    DOI 10.3389/fncel.2020.587072
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  10. Article ; Online: Synaptic release at mammalian bipolar cell terminals.

    Wan, Qun-Fang / Heidelberger, Ruth

    Visual neuroscience

    2011  Volume 28, Issue 1, Page(s) 109–119

    Abstract: Bipolar cells play a vital role in the transfer of visual information across the vertebrate retina. The synaptic output of these neurons is regulated by factors that are extrinsic and intrinsic. Relatively little is known about the intrinsic factors that ...

    Abstract Bipolar cells play a vital role in the transfer of visual information across the vertebrate retina. The synaptic output of these neurons is regulated by factors that are extrinsic and intrinsic. Relatively little is known about the intrinsic factors that regulate neurotransmitter exocytosis. Much of what we know about intrinsic presynaptic mechanisms that regulate glutamate release has come from the study of the unusually large and accessible synaptic terminal of the goldfish rod-dominant bipolar cell, the Mb1 bipolar cell. However, over the past several years, examination of presynaptic mechanisms governing neurotransmitter release has been extended to the mammalian rod bipolar cell. In this review, we discuss the recent advances in our understanding of synaptic vesicle dynamics and neurotransmitter release in rodent rod bipolar cells and consider how these properties help to shape the synaptic output of the mammalian retina.
    MeSH term(s) Animals ; Calcium Signaling/physiology ; Cytoplasm/physiology ; Endocytosis/physiology ; Excitatory Postsynaptic Potentials/physiology ; Humans ; Presynaptic Terminals/physiology ; Retina/cytology ; Retina/physiology ; Retinal Bipolar Cells/physiology ; Synapses/physiology ; Synaptic Vesicles/physiology
    Language English
    Publishing date 2011-01-28
    Publishing country England
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Review
    ZDB-ID 639436-x
    ISSN 1469-8714 ; 0952-5238
    ISSN (online) 1469-8714
    ISSN 0952-5238
    DOI 10.1017/S0952523810000453
    Database MEDical Literature Analysis and Retrieval System OnLINE

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