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Localization of the Priming Factors CAPS1 and CAPS2 in Mouse Sensory Neurons Is Determined by Their N-Termini

Both paralogs of the calcium-dependent activator protein for secretion (CAPS) are required for exocytosis of synaptic vesicles (SVs) and large dense core vesicles (LDCVs). Despite approximately 80% sequence identity, CAPS1 and CAPS2 have distinct functions in promoting exocytosis of SVs and LDCVs in...

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Autores principales: Staudt, Angelina, Ratai, Olga, Bouzouina, Aicha, Fecher-Trost, Claudia, Shaaban, Ahmed, Bzeih, Hawraa, Horn, Alexander, Shaib, Ali H., Klose, Margarete, Flockerzi, Veit, Lauterbach, Marcel A., Rettig, Jens, Becherer, Ute
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9049930/
https://www.ncbi.nlm.nih.gov/pubmed/35493323
http://dx.doi.org/10.3389/fnmol.2022.674243
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author Staudt, Angelina
Ratai, Olga
Bouzouina, Aicha
Fecher-Trost, Claudia
Shaaban, Ahmed
Bzeih, Hawraa
Horn, Alexander
Shaib, Ali H.
Klose, Margarete
Flockerzi, Veit
Lauterbach, Marcel A.
Rettig, Jens
Becherer, Ute
author_facet Staudt, Angelina
Ratai, Olga
Bouzouina, Aicha
Fecher-Trost, Claudia
Shaaban, Ahmed
Bzeih, Hawraa
Horn, Alexander
Shaib, Ali H.
Klose, Margarete
Flockerzi, Veit
Lauterbach, Marcel A.
Rettig, Jens
Becherer, Ute
author_sort Staudt, Angelina
collection PubMed
description Both paralogs of the calcium-dependent activator protein for secretion (CAPS) are required for exocytosis of synaptic vesicles (SVs) and large dense core vesicles (LDCVs). Despite approximately 80% sequence identity, CAPS1 and CAPS2 have distinct functions in promoting exocytosis of SVs and LDCVs in dorsal root ganglion (DRG) neurons. However, the molecular mechanisms underlying these differences remain enigmatic. In this study, we applied high- and super-resolution imaging techniques to systematically assess the subcellular localization of CAPS paralogs in DRG neurons deficient in both CAPS1 and CAPS2. CAPS1 was found to be more enriched at the synapses. Using – in-depth sequence analysis, we identified a unique CAPS1 N-terminal sequence, which we introduced into CAPS2. This CAPS1/2 chimera reproduced the pre-synaptic localization of CAPS1 and partially rescued synaptic transmission in neurons devoid of CAPS1 and CAPS2. Using immunoprecipitation combined with mass spectrometry, we identified CAPS1-specific interaction partners that could be responsible for its pre-synaptic enrichment. Taken together, these data suggest an important role of the CAPS1-N terminus in the localization of the protein at pre-synapses.
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spelling pubmed-90499302022-04-29 Localization of the Priming Factors CAPS1 and CAPS2 in Mouse Sensory Neurons Is Determined by Their N-Termini Staudt, Angelina Ratai, Olga Bouzouina, Aicha Fecher-Trost, Claudia Shaaban, Ahmed Bzeih, Hawraa Horn, Alexander Shaib, Ali H. Klose, Margarete Flockerzi, Veit Lauterbach, Marcel A. Rettig, Jens Becherer, Ute Front Mol Neurosci Neuroscience Both paralogs of the calcium-dependent activator protein for secretion (CAPS) are required for exocytosis of synaptic vesicles (SVs) and large dense core vesicles (LDCVs). Despite approximately 80% sequence identity, CAPS1 and CAPS2 have distinct functions in promoting exocytosis of SVs and LDCVs in dorsal root ganglion (DRG) neurons. However, the molecular mechanisms underlying these differences remain enigmatic. In this study, we applied high- and super-resolution imaging techniques to systematically assess the subcellular localization of CAPS paralogs in DRG neurons deficient in both CAPS1 and CAPS2. CAPS1 was found to be more enriched at the synapses. Using – in-depth sequence analysis, we identified a unique CAPS1 N-terminal sequence, which we introduced into CAPS2. This CAPS1/2 chimera reproduced the pre-synaptic localization of CAPS1 and partially rescued synaptic transmission in neurons devoid of CAPS1 and CAPS2. Using immunoprecipitation combined with mass spectrometry, we identified CAPS1-specific interaction partners that could be responsible for its pre-synaptic enrichment. Taken together, these data suggest an important role of the CAPS1-N terminus in the localization of the protein at pre-synapses. Frontiers Media S.A. 2022-04-14 /pmc/articles/PMC9049930/ /pubmed/35493323 http://dx.doi.org/10.3389/fnmol.2022.674243 Text en Copyright © 2022 Staudt, Ratai, Bouzouina, Fecher-Trost, Shaaban, Bzeih, Horn, Shaib, Klose, Flockerzi, Lauterbach, Rettig and Becherer. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Neuroscience
Staudt, Angelina
Ratai, Olga
Bouzouina, Aicha
Fecher-Trost, Claudia
Shaaban, Ahmed
Bzeih, Hawraa
Horn, Alexander
Shaib, Ali H.
Klose, Margarete
Flockerzi, Veit
Lauterbach, Marcel A.
Rettig, Jens
Becherer, Ute
Localization of the Priming Factors CAPS1 and CAPS2 in Mouse Sensory Neurons Is Determined by Their N-Termini
title Localization of the Priming Factors CAPS1 and CAPS2 in Mouse Sensory Neurons Is Determined by Their N-Termini
title_full Localization of the Priming Factors CAPS1 and CAPS2 in Mouse Sensory Neurons Is Determined by Their N-Termini
title_fullStr Localization of the Priming Factors CAPS1 and CAPS2 in Mouse Sensory Neurons Is Determined by Their N-Termini
title_full_unstemmed Localization of the Priming Factors CAPS1 and CAPS2 in Mouse Sensory Neurons Is Determined by Their N-Termini
title_short Localization of the Priming Factors CAPS1 and CAPS2 in Mouse Sensory Neurons Is Determined by Their N-Termini
title_sort localization of the priming factors caps1 and caps2 in mouse sensory neurons is determined by their n-termini
topic Neuroscience
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9049930/
https://www.ncbi.nlm.nih.gov/pubmed/35493323
http://dx.doi.org/10.3389/fnmol.2022.674243
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