Cited by 29Neuroscience and Neuropharmacology ResearchNicotinic Acetylcholine Receptors StudyIon channel regulation and function

Molecular Mechanism of Active Zone Organization at Vertebrate Neuromuscular Junctions

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Nishimune, Hiroshi·2012·Molecular Neurobiology

Abstract

Organization of presynaptic active zones is essential for development, plasticity, and pathology of the nervous system. Recent studies indicate a trans-synaptic molecular mechanism that organizes the active zones by connecting the pre- and the postsynaptic specialization. The presynaptic component of this trans-synaptic mechanism is comprised of cytosolic active zone proteins bound to the cytosolic domains of voltage-dependent calcium channels (P/Q-, N-, and L-type) on the presynaptic membrane. The postsynaptic component of this mechanism is the synapse organizer (laminin β2) that is expressed by the postsynaptic cell and accumulates specifically on top of the postsynaptic specialization. The pre- and the postsynaptic components interact directly between the extracellular domains of calcium channels and laminin β2 to anchor the presynaptic protein complex in front of the postsynaptic specialization. Hence, the presynaptic calcium channel functions as a scaffolding protein for active zone organization and as an ion-conducting channel for synaptic transmission. In contrast to the requirement of calcium influx for synaptic transmission, the formation of the active zone does not require the calcium influx through the calcium channels. Importantly, the active zones of adult synapses are not stable structures and require maintenance for their integrity. Furthermore, aging or diseases of the central and peripheral nervous system impair the active zones. This review will focus on the molecular mechanisms that organize the presynaptic active zones and summarize recent findings at the neuromuscular junctions and other synapses.

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Crossref · 10.1007/s12035-011-8216-y

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  • The presynaptic active zone (AZ) is a highly specialized, electron-dense region of the presynaptic membrane crucial for rapid and efficient neurotransmitter release.

    “The presynaptic active zone (AZ) is a highly specialized, electron-dense region of the presynaptic membrane crucial for rapid and efficient neurotransmitter release [11,12].”

    From Molecular Physiology of the Neuronal Synapse (2026) · cites this paper as [11]

  • Calcium influx through voltage-gated calcium channels is absolutely essential for synaptic transmission, but the initial formation of the active zone itself does not necessitate this calcium influx.

    “It is noteworthy that while calcium influx through these channels is absolutely essential for synaptic transmission, the initial formation of the active zone itself does not necessitate this calcium influx [11].”

    From Molecular Physiology of the Neuronal Synapse (2026) · cites this paper as [11]

  • On the postsynaptic side, laminin β2 is expressed by the postsynaptic cell and specifically accumulates directly opposite the postsynaptic specialization.

    “On the postsynaptic side, a key synapse organizer, laminin β2, is expressed by the postsynaptic cell and specifically accumulates directly opposite the postsynaptic specialization [11].”

    From Molecular Physiology of the Neuronal Synapse (2026) · cites this paper as [11]

  • Active zones in adult synapses are not static structures; they require continuous maintenance to preserve their integrity.

    “Active zones in adult synapses are not static structures; they require continuous maintenance to preserve their integrity [11].”

    From Molecular Physiology of the Neuronal Synapse (2026) · cites this paper as [11]

  • The extracellular domains of presynaptic calcium channels directly interact with laminin β2, anchoring the presynaptic complex in precise alignment with the postsynaptic machinery.

    “The extracellular domains of the presynaptic calcium channels directly interact with laminin β2, anchoring the presynaptic complex in precise alignment with the postsynaptic machinery.”

    From Molecular Physiology of the Neuronal Synapse (2026) · cites this paper as [11]

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Authors
Nishimune, H.
Affiliations
University of Kansas (US)
Corresponding author
Nishimune, Hiroshi
Venue
Molecular Neurobiology
Published
2011-12-02
Volume
45
Issue
1
Pages
1-16
ISSN
  • 0893-7648 (ISSN-L)
  • 1559-1182
OpenAlex
W2019314057
Cited by
29
References
202
Citations by year
2026: 2 · 2025: 1 · 2022: 1 · 2021: 1 · 2020: 1 · 2019: 6 · 2018: 2 · 2017: 2 · 2016: 4 · 2014: 3 · 2013: 1 · 2012: 5
FWCI
0.27
Type
journal article
Language
en
Open access
Locations
  • Molecular Neurobiology (publishedVersion)
  • PubMed (publishedVersion)
  • Europe PMC (PubMed Central) (acceptedVersion)
  • PubMed Central (acceptedVersion)
Funders
  • National Center for Research Resources (RR024214, P20RR024214)
  • Eunice Kennedy Shriver National Institute of Child Health and Human Development (HD002528, P30HD002528)
Topics
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Nicotinic Acetylcholine Receptors Study
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Ion channel regulation and function
Keywords
active zone, neuromuscular junction, voltage-gated calcium channels, P/Q-type calcium channels, N-type calcium channels, L-type calcium channels, laminin beta2, synaptic transmission, aging, neurodegenerative diseases
MeSH terms
Animals, Humans, Synaptic Transmission, Neuromuscular Junction, Synaptic Membranes, Vertebrates, Calcium Channels, Presynaptic Terminals, Post-Synaptic Density

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