ArticleThe Journal of biological chemistry2015
ADP ribosylation factor 6 (ARF6) promotes acrosomal exocytosis by modulating lipid turnover and Rab3A activation.
Article in The Journal of biological chemistry, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 38 citations in OpenAlex.
- An ArfGAP-dependent signaling modulates synaptic plasticity via IP3-regulated calcium release from the endoplasmic reticulum.PLoS genetics · 2026Article
- Lipid Signature of Motile Human Sperm: Characterization of Sphingomyelin, Ceramide, and Phospholipids with a Focus on Very Long Chain Polyunsaturated Fatty Acids.International journal of molecular sciences · 2025Article
- Phospholipase D1 produces phosphatidic acid at sites of secretory vesicle docking and fusion.Molecular biology of the cell · 2024Article
- Lipid remodeling in acrosome exocytosis: unraveling key players in the human sperm.Frontiers in cell and developmental biology · 2024Review
- V-ATPase modulates exocytosis in neuroendocrine cells through the activation of the ARNO-Arf6-PLD pathway and the synthesis of phosphatidic acid.Frontiers in molecular biosciences · 2023Article
- Nox1-based NADPH oxidase regulates the Par protein complex activity to control cell polarization.Frontiers in cell and developmental biology · 2023Article
- α-Synuclein is required for sperm exocytosis at a post-fusion stage.Frontiers in cell and developmental biology · 2023Article
- The pair ceramide 1-phosphate/ceramide kinase regulates intracellular calcium and progesterone-induced human sperm acrosomal exocytosis.Frontiers in cell and developmental biology · 2023Article
- Sperm Transcripts Associated With Odorant Binding and Olfactory Transduction Pathways Are Altered in Breeding Bulls Producing Poor-Quality Semen.Frontiers in veterinary science · 2022Article
- Article
- Ubiquitination-Dependent Regulation of Small GTPases in Membrane Trafficking: From Cell Biology to Human Diseases.Frontiers in cell and developmental biology · 2021Review
- Different Approaches to Record Human Sperm Exocytosis.Methods in molecular biology (Clifton, N.J.) · 2021Article
- Phosphatidic Acid: From Pleiotropic Functions to Neuronal Pathology.Frontiers in cellular neuroscience · 2019Review
- Super-resolution imaging of live sperm reveals dynamic changes of the actin cytoskeleton during acrosomal exocytosis.Journal of cell science · 2018Article
- A TEM-traceable physiologically functional gold nanoprobe that permeates non-endocytic cells.International journal of nanomedicine · 2018Article
- The Rab3A-22A Chimera Prevents Sperm Exocytosis by Stabilizing Open Fusion Pores.The Journal of biological chemistry · 2016Article
- Comparative transcript profiling of resistant and susceptible peanut post-harvest seeds in response to aflatoxin production by Aspergillus flavus.BMC plant biology · 2016Article
- Arf6 regulates the cycling and the readily releasable pool of synaptic vesicles at hippocampal synapse.eLife · 2016Article
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Authors and funding
8 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Regulated secretion is a central issue for the specific function of many cells; for instance, mammalian sperm acrosomal exocytosis is essential for egg fertilization. ARF6 (ADP-ribosylation factor 6) is a small GTPase implicated in exocytosis, but its downstream effectors remain elusive in this process. We combined biochemical, functional, and microscopy-based methods to show that ARF6 is present in human sperm, localizes to the acrosomal region, and is required for calcium and diacylglycerol-induced exocytosis. Results from pulldown assays show that ARF6 exchanges GDP for GTP in sperm challenged with different exocytic stimuli. Myristoylated and guanosine 5'-3-O-(thio)triphosphate (GTPγS)-loaded ARF6 (active form) added to permeabilized sperm induces acrosome exocytosis even in the absence of extracellular calcium. We explore the ARF6 signaling cascade that promotes secretion. We demonstrate that ARF6 stimulates a sperm phospholipase D activity to produce phosphatidic acid and boosts the synthesis of phosphatidylinositol 4,5-bisphosphate. We present direct evidence showing that active ARF6 increases phospholipase C activity, causing phosphatidylinositol 4,5-bisphosphate hydrolysis and inositol 1,4,5-trisphosphate-dependent intra-acrosomal calcium release. We show that active ARF6 increases the exchange of GDP for GTP on Rab3A, a prerequisite for secretion. We propose that exocytic stimuli activate ARF6, which is required for acrosomal calcium efflux and the assembly of the membrane fusion machinery. This report highlights the physiological importance of ARF6 as a key factor for human sperm exocytosis and fertilization.
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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.