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Role of Bassoon and Piccolo in Assembly and Molecular Organization of the Active Zone

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Gundelfinger, Eckart D., Reissner, Carsten, Garner, Craig C.·2016·Frontiers in Synaptic Neuroscience

Abstract

Bassoon and Piccolo are two very large scaffolding proteins of the cytomatrix assembled at the active zone (CAZ) where neurotransmitter is released. They share regions of high sequence similarity distributed along their entire length and seem to share both overlapping and distinct functions in organizing the CAZ. Here, we survey our present knowledge on protein-protein interactions and recent progress in understanding of molecular functions of these two giant proteins. These include roles in the assembly of active zones (AZ), the localization of voltage-gated Ca(2+) channels (VGCCs) in the vicinity of release sites, synaptic vesicle (SV) priming and in the case of Piccolo, a role in the dynamic assembly of the actin cytoskeleton. Piccolo and Bassoon are also important for the maintenance of presynaptic structure and function, as well as for the assembly of CAZ specializations such as synaptic ribbons. Recent findings suggest that they are also involved in the regulation activity-dependent communication between presynaptic boutons and the neuronal nucleus. Together these observations suggest that Bassoon and Piccolo use their modular structure to organize super-molecular complexes essential for various aspects of presynaptic function.

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  • The presynaptic active zone contains scaffolding proteins including bassoon, piccolo, RIMs, and munc13 that organize vesicle priming and the localization of voltage-gated calcium channels.

    “At the presynaptic active zone, scaffolding proteins including bassoon, piccolo, RIMs, and munc13 organize vesicle priming and the localization of voltage-gated calcium channels.”

    From Molecular Physiology of the Neuronal Synapse (2026) · cites this paper as [16]

  • Bassoon and Piccolo are integral components of the cytomatrix at the active zone (CAZ) and share significant sequence similarity, fulfilling both overlapping and distinct functions in organizing the CAZ.

    “Large scaffolding proteins, Bassoon and Piccolo, are integral components of the cytomatrix at the active zone (CAZ), the specialized region where neurotransmitter release occurs [16]. These proteins share significant sequence similarity and fulfill both overlapping and distinct functions in organizing the CAZ.”

    From Molecular Physiology of the Neuronal Synapse (2026) · cites this paper as [16]

  • Bassoon and Piccolo roles include the assembly of active zones, the precise localization of voltage-gated Ca2+ channels near release sites, and synaptic vesicle priming.

    “Their roles include the assembly of active zones, the precise localization of voltage-gated Ca2+ channels near release sites, and synaptic vesicle priming [15,16].”

    From Molecular Physiology of the Neuronal Synapse (2026) · cites this paper as [16]

  • Activated DAPK1 phosphorylates GluN2B at Ser-1303, enhancing channel conductance and leading to detrimental calcium influx.

    “Activated DAPK1 phosphorylates GluN2B at Ser-1303, enhancing channel conductance and leading to detrimental calcium influx.16”

    From Molecular Physiology of the Neuronal Synapse (2026) · cites this paper as [16]

    The Introduction discusses Bassoon interactions and presynaptic calcium channels, not DAPK1 or GluN2B phosphorylation. Searches for DAPK1, GluN2B, Ser-1303, channel conductance, and calcium influx found no passage in our copy addressing the claimed mechanism. (LLM, conf=0.76)

    Experimental — accuracy not yet measured
  • Synaptic retention of GluN2A requires its CTD for stable interactions with PDZ domain-containing scaffolding molecules like PSD-95.

    “Synaptic retention of GluN2A requires its CTD for stable interactions with PDZ domain-containing scaffolding molecules like PSD-95.16”

    From Molecular Physiology of the Neuronal Synapse (2026) · cites this paper as [16]

    The paper’s “Synapse Maintenance and integrity” section discusses the presynaptic roles of Bassoon and Piccolo, not GluN2A retention. Searches for GluN2A, its C-terminal domain, PDZ scaffolds, and PSD-95 found no passage in our copy addressing the claimed interaction; the nearby matches are references, not evidence for the claim. No page number is available for the cited section. (LLM, conf=0.76)

    Experimental — accuracy not yet measured

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Authors
Gundelfinger, E. D., Reissner, C., & Garner, C. C.
Affiliations
  • German Center for Neurodegenerative Diseases (DE)
  • University of Münster (DE)
Corresponding author
  • Gundelfinger, Eckart D.
  • Garner, Craig C.
Venue
Frontiers in Synaptic Neuroscience
Published
2016-01-12
Volume
7
Pages
19-19
ISSN
1663-3563 (ISSN-L)
OpenAlex
W2256900453
Cited by
203
References
130
Citations by year
2026: 12 · 2025: 15 · 2024: 21 · 2023: 22 · 2022: 32 · 2021: 16 · 2020: 15 · 2019: 24 · 2018: 18 · 2017: 18 · 2016: 10
FWCI
2.55
Type
journal article
Language
en
Open access
Licence
cc-by
Locations
  • Frontiers in Synaptic Neuroscience (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
  • Informationszentrum Lebenswissenschaften (ZB MED) (submittedVersion, cc-by)
  • DZNE Pub (submittedVersion, other-oa)
Funders
  • Australian Government
  • European Commission
  • Deutsche Forschungsgemeinschaft (SFB 665, SFB 779, SFB 958, SFB-854)
  • Bundesministerium für Bildung und Forschung
  • Deutsches Zentrum für Neurodegenerative Erkrankungen
  • Leibniz-Gemeinschaft (SFB779)
Topics
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular transport and secretion
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetics and Neurodevelopmental Disorders
Keywords
bassoon, piccolo, active zone, protein-protein interaction, voltage-gated calcium channels, synaptic vesicle priming, actin cytoskeleton, synaptic ribbons, neurotransmitter release, activity-dependent synaptic plasticity

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