The synapsins: Key actors of synapse function and plasticity

Cesca, Fabrizia; Baldelli, Pietro; Valtorta, Flavia; Benfenati, Fabio

doi:10.1016/j.pneurobio.2010.04.006

Cited by 560 publications

(631 citation statements)

References 371 publications

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“…In most cases, synapsins were phosphorylated at site 1 (Ser9 in synapsin 1, Ser10 in synapsin 2), a site phosphorylated upon depolarization following Ca 2+ influx. Other identified phosphorylations encompassed sites 4, 5, 6, and 7 [14]. Thus, out of eight functionally characterized phosphorylation sites in synapsins, six were present in the protein iso-spots accumulating in the SORLA-deficient cortex.…”

Section: Phosphorylated Synapsins Accumulate In the Brain Of Sorla-dementioning

confidence: 92%

“…1). Antibodies directed against synapsins phosphorylated at sites 1, 4, and 6 correspond to anti-phospho-synapsin (Ser9), anti-phospho-synapsin 1 (Ser62), and anti-phospho-synapsin 1 (Ser549), respectively, according to the originally identified phosphorylation sites in the rat [14]. Antibodies directed against 14-3-3 binding motifs correspond to motif 1 (Arg/Lys and Ser at positions -3 and -2, phospho-Ser at position 0, and Pro at position +2; "motif a", polyclonal antibody; "motif b, monoclonal antibody) and motif 2 (Phospho-(Ser) Arg-X-Tyr/Phe-X-pSer; "motif c"), respectively [37].…”

Section: Methodsmentioning

confidence: 99%

“…Typically, phosphorylation induces mobilization of SV that are sequestered by synapsins otherwise (reviewed in [14]). Because accumulation of synapsins was seen for multiple iso-spots in our 2-D gels, indicative of alternative post-translational modification, we tested the phosphorylation status of these synapsin isoforms using NanoLC-ESI-MS/MS mass spectrometry.…”

Section: Phosphorylated Synapsins Accumulate In the Brain Of Sorla-dementioning

confidence: 99%

“…The phosphorylation sites identified for the respective iso-spots by NanoLC-ESI-MS/MS mass spectrometry are also given. Numbers in brackets refer to the numbering of synapsin phosphorylation sites 1 through 8 as described in [14]. A slash between two modification sites indicates that an unambiguous assignment of phosphorylation site was not possible.…”

Section: Statistical Analysesmentioning

confidence: 99%

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SORLA regulates calpain‐dependent degradation of synapsin

Hartl

Nebrich

Klein

et al. 2016

Alzheimer's & Dementia

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IntroductionSorting‐related receptor with A‐type repeats (SORLA) is an intracellular sorting receptor in neurons and a major risk factor for Alzheimer disease.MethodsHere, we performed global proteome analyses in the brain of SORLA‐deficient mice followed by biochemical and histopathologic studies to identify novel neuronal pathways affected by receptor dysfunction.ResultsWe demonstrate that the lack of SORLA results in accumulation of phosphorylated synapsins in cortex and hippocampus. We propose an underlying molecular mechanism by demonstrating that SORLA interacts with phosphorylated synapsins through 14‐3‐3 adaptor proteins to deliver synapsins to calpain‐mediated proteolytic degradation.DiscussionOur results suggest a novel function for SORLA which is in control of synapsin degradation, potentially impacting on synaptic vesicle endocytosis and/or exocytosis.

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Section: Phosphorylated Synapsins Accumulate In the Brain Of Sorla-dementioning

confidence: 92%

Section: Methodsmentioning

confidence: 99%

Section: Phosphorylated Synapsins Accumulate In the Brain Of Sorla-dementioning

confidence: 99%

Section: Statistical Analysesmentioning

confidence: 99%

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SORLA regulates calpain‐dependent degradation of synapsin

Hartl

Nebrich

Klein

et al. 2016

Alzheimer's & Dementia

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“…The Ca 2þ /CaM-activated protein kinase ('CaM kinase') is important for neurotransmission, because it regulates, by phosphorylation of synapsin, the release of vesicles from the actin web, thus facilitating their access to the cell membrane [158]. During evolution, CaM kinase has been maintained only in monokonts from myxamoebae Dictyostelium to man [159].…”

Section: Molecular Targets Of Ca 2þ In Cellsmentioning

confidence: 99%

Inseparable tandem: evolution chooses ATP and Ca²⁺to control life, death and cellular signalling

Plattner

Verkhratsky

2016

Phil. Trans. R. Soc. B

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From the very dawn of biological evolution, ATP was selected as a multipurpose energy-storing molecule. Metabolism of ATP required intracellular free Ca 2þ to be set at exceedingly low concentrations, which in turn provided the background for the role of Ca 2þ as a universal signalling molecule. The early-eukaryote life forms also evolved functional compartmentalization and vesicle trafficking, which used Ca 2þ as a universal signalling ion; similarly, Ca 2þ is needed for regulation of ciliary and flagellar beat, amoeboid movement, intracellular transport, as well as of numerous metabolic processes. Thus, during evolution, exploitation of atmospheric oxygen and increasingly efficient ATP production via oxidative phosphorylation by bacterial endosymbionts were a first step for the emergence of complex eukaryotic cells. Simultaneously, Ca 2þ started to be exploited for shortrange signalling, despite restrictions by the preset phosphate-based energy metabolism, when both phosphates and Ca 2þ interfere with each other because of the low solubility of calcium phosphates. The need to keep cytosolic Ca 2þ low forced cells to restrict Ca 2þ signals in space and time and to develop energetically favourable Ca 2þ signalling and Ca 2þ microdomains. These steps in tandem dominated further evolution. The ATP molecule (often released by Ca 2þ -regulated exocytosis) rapidly grew to be the universal chemical messenger for intercellular communication; ATP effects are mediated by an extended family of purinoceptors often linked to Ca 2þ signalling. Similar to atmospheric oxygen, Ca 2þ must have been reverted from a deleterious agent to a most useful (intra-and extracellular) signalling molecule. Invention of intracellular trafficking further increased the role for Ca 2þ homeostasis that became critical for regulation of cell survival and cell death. Several mutually interdependent effects of Ca 2þ and ATP have been exploited in evolution, thus turning an originally unholy alliance into a fascinating success story.This article is part of the themed issue 'Evolution brings Ca 2þ and ATP together to control life and death'.

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