ArticleMolecular biology of the cell2014
NAADP and the two-pore channel protein 1 participate in the acrosome reaction in mammalian spermatozoa.
Article in Molecular biology of the cell, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.
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Who cites it
33 citing papers in PubMed, 56 citations in OpenAlex.
- Review
- Structure and Function of Plant and Mammalian TPC Channels.Handbook of experimental pharmacology · 2023Article
- Two-pore channel blockade by phosphoinositide kinase inhibitors YM201636 and PI-103 determined by a histidine residue near pore-entrance.Communications biology · 2022Article
- A genetically targeted sensor reveals spatial and temporal dynamics of acrosomal calcium and sperm acrosome exocytosis.The Journal of biological chemistry · 2022Article
- Two-Pore Channels Regulate Inter-Organellar CaCells · 2022Review
- Autophagy: a multifaceted player in the fate of sperm.Human reproduction update · 2022Review
- Review
- Whole-Genome Sequencing and Characterization of Buffalo Genetic Resources: Recent Advances and Future Challenges.Animals : an open access journal from MDPI · 2021Review
- Two-pore channels affect EGF receptor signaling by receptor trafficking and expression.iScience · 2021Article
- Genetic Inactivation of Two-Pore Channel 1 Impairs Spatial Learning and Memory.Behavior genetics · 2020Article
- Targeting Two-Pore Channels: Current Progress and Future Challenges.Trends in pharmacological sciences · 2020Review
- TPC1 deficiency or blockade augments systemic anaphylaxis and mast cell activity.Proceedings of the National Academy of Sciences of the United States of America · 2020Article
- Role of Two-Pore Channels in Embryonic Development and Cellular Differentiation.Cold Spring Harbor perspectives in biology · 2020Review
- [Bioinformatics analysis of expression and function of EXD3 gene in gastric cancer].Nan fang yi ke da xue xue bao = Journal of Southern Medical University · 2019Article
- Two-pore channels and disease.Biochimica et biophysica acta. Molecular cell research · 2018Review
- Structural insights into the voltage and phospholipid activation of the mammalian TPC1 channel.Nature · 2018Article
- TPC2 polymorphisms associated with a hair pigmentation phenotype in humans result in gain of channel function by independent mechanisms.Proceedings of the National Academy of Sciences of the United States of America · 2017Article
- Ned-19 inhibition of parasite growth and multiplication suggests a role for NAADP mediated signalling in the asexual development of Plasmodium falciparum.Malaria journal · 2017Article
- The two-pore channel TPC1 is required for efficient protein processing through early and recycling endosomes.Scientific reports · 2017Article
- Loss of the NaThe Journal of biological chemistry · 2017Article
Corrections and comments
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Authors and funding
14 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
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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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.