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NAADP and the two-pore channel protein 1 participate in the acrosome reaction in mammalian spermatozoa

The functional relationship between the formation of hundreds of fusion pores during the acrosome reaction in spermatozoa and the mobilization of calcium from the acrosome has been determined only partially. Hence, the second messenger NAADP, promoting efflux of calcium from lysosome-like compartmen...

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Autores principales: Arndt, Lilli, Castonguay, Jan, Arlt, Elisabeth, Meyer, Dorke, Hassan, Sami, Borth, Heike, Zierler, Susanna, Wennemuth, Gunther, Breit, Andreas, Biel, Martin, Wahl-Schott, Christian, Gudermann, Thomas, Klugbauer, Norbert, Boekhoff, Ingrid
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The American Society for Cell Biology 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3952862/
https://www.ncbi.nlm.nih.gov/pubmed/24451262
http://dx.doi.org/10.1091/mbc.E13-09-0523
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author Arndt, Lilli
Castonguay, Jan
Arlt, Elisabeth
Meyer, Dorke
Hassan, Sami
Borth, Heike
Zierler, Susanna
Wennemuth, Gunther
Breit, Andreas
Biel, Martin
Wahl-Schott, Christian
Gudermann, Thomas
Klugbauer, Norbert
Boekhoff, Ingrid
author_facet Arndt, Lilli
Castonguay, Jan
Arlt, Elisabeth
Meyer, Dorke
Hassan, Sami
Borth, Heike
Zierler, Susanna
Wennemuth, Gunther
Breit, Andreas
Biel, Martin
Wahl-Schott, Christian
Gudermann, Thomas
Klugbauer, Norbert
Boekhoff, Ingrid
author_sort Arndt, Lilli
collection PubMed
description The functional relationship between the formation of hundreds of fusion pores during the acrosome reaction in spermatozoa and the mobilization of calcium from the acrosome has been determined only partially. Hence, the second messenger NAADP, promoting efflux of calcium from lysosome-like compartments and one of its potential molecular targets, the two-pore channel 1 (TPC1), were analyzed for its involvement in triggering the acrosome reaction using a TPCN1 gene–deficient mouse strain. The present study documents that TPC1 and NAADP-binding sites showed a colocalization at the acrosomal region and that treatment of spermatozoa with NAADP resulted in a loss of the acrosomal vesicle that showed typical properties described for TPCs: Registered responses were not detectable for its chemical analogue NADP and were blocked by the NAADP antagonist trans-Ned-19. In addition, two narrow bell-shaped dose-response curves were identified with maxima in either the nanomolar or low micromolar NAADP concentration range, where TPC1 was found to be responsible for activating the low affinity pathway. Our finding that two convergent NAADP-dependent pathways are operative in driving acrosomal exocytosis supports the concept that both NAADP-gated cascades match local NAADP concentrations with the efflux of acrosomal calcium, thereby ensuring complete fusion of the large acrosomal vesicle.
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spelling pubmed-39528622014-05-30 NAADP and the two-pore channel protein 1 participate in the acrosome reaction in mammalian spermatozoa Arndt, Lilli Castonguay, Jan Arlt, Elisabeth Meyer, Dorke Hassan, Sami Borth, Heike Zierler, Susanna Wennemuth, Gunther Breit, Andreas Biel, Martin Wahl-Schott, Christian Gudermann, Thomas Klugbauer, Norbert Boekhoff, Ingrid Mol Biol Cell Articles The functional relationship between the formation of hundreds of fusion pores during the acrosome reaction in spermatozoa and the mobilization of calcium from the acrosome has been determined only partially. Hence, the second messenger NAADP, promoting efflux of calcium from lysosome-like compartments and one of its potential molecular targets, the two-pore channel 1 (TPC1), were analyzed for its involvement in triggering the acrosome reaction using a TPCN1 gene–deficient mouse strain. The present study documents that TPC1 and NAADP-binding sites showed a colocalization at the acrosomal region and that treatment of spermatozoa with NAADP resulted in a loss of the acrosomal vesicle that showed typical properties described for TPCs: Registered responses were not detectable for its chemical analogue NADP and were blocked by the NAADP antagonist trans-Ned-19. In addition, two narrow bell-shaped dose-response curves were identified with maxima in either the nanomolar or low micromolar NAADP concentration range, where TPC1 was found to be responsible for activating the low affinity pathway. Our finding that two convergent NAADP-dependent pathways are operative in driving acrosomal exocytosis supports the concept that both NAADP-gated cascades match local NAADP concentrations with the efflux of acrosomal calcium, thereby ensuring complete fusion of the large acrosomal vesicle. The American Society for Cell Biology 2014-03-15 /pmc/articles/PMC3952862/ /pubmed/24451262 http://dx.doi.org/10.1091/mbc.E13-09-0523 Text en © 2014 Arndt et al. This article is distributed by The American Society for Cell Biology under license from the author(s). Two months after publication it is available to the public under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License (http://creativecommons.org/licenses/by-nc-sa/3.0). “ASCB®,” “The American Society for Cell Biology®,” and “Molecular Biology of the Cell®” are registered trademarks of The American Society of Cell Biology.
spellingShingle Articles
Arndt, Lilli
Castonguay, Jan
Arlt, Elisabeth
Meyer, Dorke
Hassan, Sami
Borth, Heike
Zierler, Susanna
Wennemuth, Gunther
Breit, Andreas
Biel, Martin
Wahl-Schott, Christian
Gudermann, Thomas
Klugbauer, Norbert
Boekhoff, Ingrid
NAADP and the two-pore channel protein 1 participate in the acrosome reaction in mammalian spermatozoa
title NAADP and the two-pore channel protein 1 participate in the acrosome reaction in mammalian spermatozoa
title_full NAADP and the two-pore channel protein 1 participate in the acrosome reaction in mammalian spermatozoa
title_fullStr NAADP and the two-pore channel protein 1 participate in the acrosome reaction in mammalian spermatozoa
title_full_unstemmed NAADP and the two-pore channel protein 1 participate in the acrosome reaction in mammalian spermatozoa
title_short NAADP and the two-pore channel protein 1 participate in the acrosome reaction in mammalian spermatozoa
title_sort naadp and the two-pore channel protein 1 participate in the acrosome reaction in mammalian spermatozoa
topic Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3952862/
https://www.ncbi.nlm.nih.gov/pubmed/24451262
http://dx.doi.org/10.1091/mbc.E13-09-0523
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