ArticleScientific reports2016
Thrombospondin-4 reduces binding affinity of [(3)H]-gabapentin to calcium-channel α2δ-1-subunit but does not interact with α2δ-1 on the cell-surface when co-expressed.
Article in Scientific reports, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.
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Who cites it
31 citing papers in PubMed, 40 citations in OpenAlex.
- Molecular Partners of Voltage-Gated Calcium Channel β and αThe Journal of membrane biology · 2026Review
- Biochemistry and physiology of voltage-gated calcium channel trafficking: a target for gabapentinoid drugs.Open biology · 2025Review
- α2δ-1-Linked NMDA and AMPA Receptors in Neuropathic Pain and Gabapentinoid Action.Journal of neurochemistry · 2025Review
- Novel insights into the multifaceted and tissue-specific roles of the endocytic receptor LRP1.The Journal of biological chemistry · 2024Review
- The role of voltage-gated calcium channel α2δ-1 in the occurrence and development in myofascial orofacial pain.BMC oral health · 2024Article
- The α2δ-1-NMDA receptor complex and its potential as a therapeutic target for ischemic stroke.Frontiers in neurology · 2023Review
- Pathophysiological Roles of Auxiliary Calcium Channel αHandbook of experimental pharmacology · 2023Article
- Pregabalin for chemotherapy-induced neuropathy: background and rationale for further study.Supportive care in cancer : official journal of the Multinational Association of Supportive Care in Cancer · 2022Review
- Calcium Channels in Retinal Function and Disease.Annual review of vision science · 2022Review
- Novel Therapies for the Treatment of Neuropathic Pain: Potential and Pitfalls.Journal of clinical medicine · 2022Review
- Rab11-dependent recycling of calcium channels is mediated by auxiliary subunit αScientific reports · 2021Article
- The Calcium Channel α2δ1 Subunit: Interactional Targets in Primary Sensory Neurons and Role in Neuropathic Pain.Frontiers in cellular neuroscience · 2021Review
- Presynaptic calcium channels: specialized control of synaptic neurotransmitter release.Nature reviews. Neuroscience · 2020Review
- Defining the Adult Neural Stem Cell Niche Proteome Identifies Key Regulators of Adult Neurogenesis.Cell stem cell · 2020Article
- Direct, gabapentin-insensitive interaction of a soluble form of the calcium channel subunit αScientific reports · 2019Article
- Specific factors in blood from young but not old mice directly promote synapse formation and NMDA-receptor recruitment.Proceedings of the National Academy of Sciences of the United States of America · 2019Article
- Increased α2δ-1-NMDA receptor coupling potentiates glutamatergic input to spinal dorsal horn neurons in chemotherapy-induced neuropathic pain.Journal of neurochemistry · 2019Article
- Ablation of αProceedings of the National Academy of Sciences of the United States of America · 2018Article
- The α2δ-1-NMDA receptor coupling is essential for corticostriatal long-term potentiation and is involved in learning and memory.The Journal of biological chemistry · 2018Article
- CACHD1 is an α2δ-Like Protein That Modulates CaThe Journal of neuroscience : the official journal of the Society for Neuroscience · 2018Article
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
The α2δ proteins are auxiliary subunits of voltage-gated calcium channels, and influence their trafficking and biophysical properties. The α2δ ligand gabapentin interacts with α2δ-1, and inhibits calcium channel trafficking. However, α2-1 has also been proposed to play a synaptogenic role, independent of calcium channel function. In this regard, α2δ-1 was identified as a ligand of thrombospondins, with the interaction involving the thrombospondin synaptogenic domain and the α2δ-1 von-Willebrand-factor domain. Co-immunoprecipitation between α2δ-1 and the synaptogenic domain of thrombospondin-2 was prevented by gabapentin. We therefore examined whether interaction of thrombospondin with α2δ-1 might reciprocally influence (3)H-gabapentin binding. We concentrated on thrombospondin-4, because, like α2δ-1, it is upregulated in neuropathic pain models. We found that in membranes from cells co-transfected with α2δ-1 and thrombospondin-4, there was a Mg(2+) -dependent reduction in affinity of (3)H-gabapentin binding to α2δ-1. This effect was lost for α2δ-1 with mutations in the von-Willebrand-factor-A domain. However, the effect on (3)H-gabapentin binding was not reproduced by the synaptogenic EGF-domain of thrombospondin-4. Partial co-immunoprecipitation could be demonstrated between thrombospondin-4 and α2δ-1 when co-transfected, but there was no co-immunoprecipitation with thrombospondin-4-EGF domain. Furthermore, we could not detect any association between these two proteins on the cell-surface, indicating the demonstrated interaction occurs intracellularly.
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