Angiotensin-Receptor-Associated Protein Modulates Ca2+ Signals in Photoreceptor and Mossy Fiber cells

Rene Barro-Soria; Alejandro Caicedo; Herbert Jägle; Laura Merkel; Na Zhao; Gabriel Knop; Kaspar Gierke; Andrea Dannullis; Hayo Castrop; Johann Helmut Brandstätter; Frank Kirchhoff; Andreas Feigenspan; Olaf Strauß

doi:10.1038/s41598-019-55380-8

Angiotensin-Receptor-Associated Protein Modulates Ca²⁺ Signals in Photoreceptor and Mossy Fiber cells

Rene Barro-Soria, Alejandro Caicedo, Herbert Jägle, Laura Merkel, Na Zhao, Gabriel Knop, Kaspar Gierke, Andrea Dannullis, Hayo Castrop, Johann Helmut Brandstätter, Frank Kirchhoff, Andreas Feigenspan, Olaf Strauß

Medicine

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Abstract

Fast, precise and sustained neurotransmission requires graded Ca²⁺ signals at the presynaptic terminal. Neurotransmitter release depends on a complex interplay of Ca²⁺ fluxes and Ca²⁺ buffering in the presynaptic terminal that is not fully understood. Here, we show that the angiotensin-receptor-associated protein (ATRAP) localizes to synaptic terminals throughout the central nervous system. In the retinal photoreceptor synapse and the cerebellar mossy fiber-granule cell synapse, we find that ATRAP is involved in the generation of depolarization-evoked synaptic Ca²⁺ transients. Compared to wild type, Ca²⁺ imaging in acutely isolated preparations of the retina and the cerebellum from ATRAP knockout mice reveals a significant reduction of the sarcoendoplasmic reticulum (SR) Ca²⁺-ATPase (SERCA) activity. Thus, in addition to its conventional role in angiotensin signaling, ATRAP also modulates presynaptic Ca²⁺ signaling within the central nervous system.

Original language	English (US)
Article number	19622
Journal	Scientific reports
Volume	9
Issue number	1
DOIs	https://doi.org/10.1038/s41598-019-55380-8
State	Published - Dec 1 2019

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Angiotensin-Receptor-Associated Protein Modulates Ca²⁺ Signals in Photoreceptor and Mossy Fiber cells. / Barro-Soria, Rene ; Caicedo, Alejandro; Jägle, Herbert; Merkel, Laura; Zhao, Na; Knop, Gabriel; Gierke, Kaspar; Dannullis, Andrea; Castrop, Hayo; Brandstätter, Johann Helmut; Kirchhoff, Frank; Feigenspan, Andreas; Strauß, Olaf.

In: Scientific reports, Vol. 9, No. 1, 19622, 01.12.2019.

Research output: Contribution to journal › Article › peer-review

Barro-Soria, Rene ; Caicedo, Alejandro ; Jägle, Herbert ; Merkel, Laura ; Zhao, Na ; Knop, Gabriel ; Gierke, Kaspar ; Dannullis, Andrea ; Castrop, Hayo ; Brandstätter, Johann Helmut ; Kirchhoff, Frank ; Feigenspan, Andreas ; Strauß, Olaf. / Angiotensin-Receptor-Associated Protein Modulates Ca²⁺ Signals in Photoreceptor and Mossy Fiber cells. In: Scientific reports. 2019 ; Vol. 9, No. 1.

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title = "Angiotensin-Receptor-Associated Protein Modulates Ca2+ Signals in Photoreceptor and Mossy Fiber cells",

abstract = "Fast, precise and sustained neurotransmission requires graded Ca2+ signals at the presynaptic terminal. Neurotransmitter release depends on a complex interplay of Ca2+ fluxes and Ca2+ buffering in the presynaptic terminal that is not fully understood. Here, we show that the angiotensin-receptor-associated protein (ATRAP) localizes to synaptic terminals throughout the central nervous system. In the retinal photoreceptor synapse and the cerebellar mossy fiber-granule cell synapse, we find that ATRAP is involved in the generation of depolarization-evoked synaptic Ca2+ transients. Compared to wild type, Ca2+ imaging in acutely isolated preparations of the retina and the cerebellum from ATRAP knockout mice reveals a significant reduction of the sarcoendoplasmic reticulum (SR) Ca2+-ATPase (SERCA) activity. Thus, in addition to its conventional role in angiotensin signaling, ATRAP also modulates presynaptic Ca2+ signaling within the central nervous system.",

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note = "Funding Information: Tg(Rac3-EGFP)JZ58Gsat/Mmcd (Rac3-EGFP) mice were obtained from the Mutant Mouse Regional Resource Center, a NCRR-NIH funded strain repository, and were donated to the MMRRC by the NINDS funded GENSAT BAC transgenic project. Funding Information: The authors thank the excellent technical expertise of Elfriede Eckert (Experimental Ophthalmologe Regensburg) and Bernhard Gess (Institute of Physiology Regensburg).This work has been funded by the Deutsche Forschungsgemeinschaft (DFG) grant SFB699, subprojects B7 (Castrop) and B8 (Strau{\ss}). We acknowledge support from the German Research Foundation (DFG) and the Open Access Publications Fonds of the Charite - Universit{\"a}tsmedizin Berlin. Publisher Copyright: {\textcopyright} 2019, The Author(s).",

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AU - Barro-Soria, Rene

AU - Caicedo, Alejandro

AU - Jägle, Herbert

AU - Merkel, Laura

AU - Zhao, Na

AU - Knop, Gabriel

AU - Gierke, Kaspar

AU - Dannullis, Andrea

AU - Castrop, Hayo

AU - Brandstätter, Johann Helmut

AU - Kirchhoff, Frank

AU - Feigenspan, Andreas

AU - Strauß, Olaf

N1 - Funding Information: Tg(Rac3-EGFP)JZ58Gsat/Mmcd (Rac3-EGFP) mice were obtained from the Mutant Mouse Regional Resource Center, a NCRR-NIH funded strain repository, and were donated to the MMRRC by the NINDS funded GENSAT BAC transgenic project. Funding Information: The authors thank the excellent technical expertise of Elfriede Eckert (Experimental Ophthalmologe Regensburg) and Bernhard Gess (Institute of Physiology Regensburg).This work has been funded by the Deutsche Forschungsgemeinschaft (DFG) grant SFB699, subprojects B7 (Castrop) and B8 (Strauß). We acknowledge support from the German Research Foundation (DFG) and the Open Access Publications Fonds of the Charite - Universitätsmedizin Berlin. Publisher Copyright: © 2019, The Author(s).

PY - 2019/12/1

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N2 - Fast, precise and sustained neurotransmission requires graded Ca2+ signals at the presynaptic terminal. Neurotransmitter release depends on a complex interplay of Ca2+ fluxes and Ca2+ buffering in the presynaptic terminal that is not fully understood. Here, we show that the angiotensin-receptor-associated protein (ATRAP) localizes to synaptic terminals throughout the central nervous system. In the retinal photoreceptor synapse and the cerebellar mossy fiber-granule cell synapse, we find that ATRAP is involved in the generation of depolarization-evoked synaptic Ca2+ transients. Compared to wild type, Ca2+ imaging in acutely isolated preparations of the retina and the cerebellum from ATRAP knockout mice reveals a significant reduction of the sarcoendoplasmic reticulum (SR) Ca2+-ATPase (SERCA) activity. Thus, in addition to its conventional role in angiotensin signaling, ATRAP also modulates presynaptic Ca2+ signaling within the central nervous system.

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Angiotensin-Receptor-Associated Protein Modulates Ca²⁺ Signals in Photoreceptor and Mossy Fiber cells

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