The dephosphins: dephosphorylation by calcineurin triggers synaptic vesicle endocytosis
Abstract
When nerve terminals in the brain are stimulated, a group of phosphoproteins called the dephosphins are coordinately dephosphorylated by calcineurin, the Ca(2+)-dependent protein phosphatase. Amazingly, the seven presently known dephosphins are not structurally related, yet each has been independently shown to be essential for synaptic vesicle endocytosis (SVE). Nowhere else in biology is there a similar example of the coordinated dephosphorylation of such a large group of proteins each sharing roles in the same biological response. This suggests that dephosphorylation and phosphorylation of the dephosphins is essential for SVE. Recent studies in synaptosomes have confirmed this view, with calcineurin-mediated dephosphorylation of the dephosphins essential for triggering SVE. The phosphorylation cycle of the dephosphins might regulate SVE by targeting the proteins to sites of action and by stimulating the assembly of several large essential endocytic protein complexes.
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The BIN1 and DAB1 genes are noteworthy loci implicated by the data.
“Also noteworthy are the bridging integrator 1 (BIN1) gene, which produces a protein involved in synaptic vesicle endoctyosis 13 , and the disabled homolog 1 (DAB1) gene, whose product is involved with tyrosine phosphorylation and microtubule function in neurons 14 .”
From Genome-wide association study identifies variants at CLU and PICALM associated with Alzheimer's disease (2009) · cites this paper as [14]
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“Central to this mechanism is the coordinated dephosphorylation of a subset of endocytosis proteins called the dephosphins, by the calcium-dependent protein phosphatase calcineurin (Clayton and Cousin 2009; Cousin and Robinson 2001; Imoto et al. 2022, 2024).”
Self-citation
- Authors
- Cousin, M. A., & Robinson, P. J.
- Affiliations
- University of Edinburgh (GB)
- Children's Medical Research Institute (AU)
- Corresponding author
- Robinson, Phillip J
- Venue
- Trends in Neurosciences
- Publisher
- Elsevier BV
- Published
- 2001-11
- Volume
- 24
- Issue
- 11
- Pages
- 659-665
- ISSN
- 0166-2236 (ISSN-L)
- OpenAlex
- W2035336615
- Cited by
- 330
- References
- 2
- Citations by year
- 2026: 3 · 2025: 10 · 2024: 7 · 2023: 8 · 2022: 8 · 2021: 10 · 2020: 5 · 2019: 9 · 2018: 13 · 2017: 14 · 2016: 10 · 2015: 6 · 2014: 19 · 2013: 14 · 2012: 22
- FWCI
- 1.02
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Trends in Neurosciences (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular transport and secretion
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Signaling Pathways in Disease
- Keywords
- calcineurin, synaptic vesicle endocytosis, protein dephosphorylation, synaptosomes, presynaptic terminals, synaptic plasticity
- MeSH terms
- Animals, Endocytosis, Phosphorylation, Synaptic Vesicles, Calcineurin, GTP Phosphohydrolases, Dynamins
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