Piccolo and bassoon maintain synaptic vesicle clustering without directly participating in vesicle exocytosis
Open accessAbstract
Piccolo and bassoon are highly homologous multidomain proteins of the presynaptic cytomatrix whose function is unclear. Here, we generated piccolo knockin/knockout mice that either contain wild-type levels of mutant piccolo unable to bind Ca(2+) (knockin), approximately 60% decreased levels of piccolo that is C-terminally truncated (partial knockout), or <5% levels of piccolo (knockout). All piccolo mutant mice were viable and fertile, but piccolo knockout mice exhibited increased postnatal mortality. Unexpectedly, electrophysiology and electron microscopy of piccolo-deficient synapses failed to uncover a major phenotype either in acute hippocampal slices or in cultured cortical neurons. To unmask potentially redundant functions of piccolo and bassoon, we thus acutely knocked down expression of bassoon in wild-type and piccolo knockout neurons. Despite a nearly complete loss of piccolo and bassoon, however, we still did not detect an electrophysiological phenotype in cultured piccolo- and bassoon-deficient neurons in either GABAergic or glutamatergic synaptic transmission. In contrast, electron microscopy revealed a significant reduction in synaptic vesicle clustering in double bassoon/piccolo-deficient synapses. Thus, we propose that piccolo and bassoon play a redundant role in synaptic vesicle clustering in nerve terminals without directly participating in neurotransmitter release.
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Piccolo and bassoon are large proteins specific to vertebrates whose major function appears to be to guide synaptic vesicles from the backfield of the synapse to the active zone.
“Piccolo and bassoon are large proteins specific to vertebrates whose major function appears to be to guide synaptic vesicles from the backfield of the synapse to the active zone (Mukherjee et al., 2010; Hallermann et al., 2010).”
From The Presynaptic Active Zone (2012) · cites this paper as Mukherjee et al., 2010
In synapses with a partial loss of both piccolo and bassoon, synaptic vesicle clusters are disrupted.
“In synapses with a partial loss of both piccolo and bassoon, synaptic vesicle clusters are disrupted”
From The Presynaptic Active Zone (2012) · cites this paper as Mukherjee et al., 2010
Deletion of piccolo has no significant effect on survival or on neurotransmitter release in cultured neurons or in acute slices.
“deletion of piccolo has no significant effect on survival or on neurotransmitter release in cultured neurons or in acute slices (Mukherjee et al., 2010).”
From The Presynaptic Active Zone (2012) · cites this paper as Mukherjee et al., 2010
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Piccolo, a presynaptic zinc finger protein structurally related to bassoon
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Central presynaptic terminals are enriched in ATP but the majority lack mitochondria
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- Authors
- Mukherjee, K., Yang, X., Gerber, S. H., Kwon, H.-B., Ho, A., Castillo, P. E., Liu, X., & Südhof, T. C.
- Affiliations
- Stanford University (US)
- The University of Texas Southwestern Medical Center (US)
- Heidelberg University (DE)
- Albert Einstein College of Medicine (US)
- Howard Hughes Medical Institute (US)
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 2010-03-23
- Volume
- 107
- Issue
- 14
- Pages
- 6504-6509
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC2851964
- OpenAlex
- W2030094319
- Cited by
- 195
- References
- 6
- Citations by year
- 2026: 6 · 2025: 8 · 2024: 8 · 2023: 12 · 2022: 8 · 2021: 10 · 2020: 12 · 2019: 16 · 2018: 12 · 2017: 11 · 2016: 10 · 2015: 11 · 2014: 15 · 2013: 17 · 2012: 16
- FWCI
- 7.10
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Howard Hughes Medical Institute
- Deutsche Forschungsgemeinschaft
- National Institute on Drug Abuse
- 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
- piccolo, bassoon, synaptic vesicle clustering, synaptic vesicle exocytosis, neurotransmitter release, synaptic transmission, calcium binding, functional redundancy, GABAergic synapses, glutamatergic synapses, postnatal mortality
- MeSH terms
- Amino Acid Sequence, Animals, Cytoskeletal Proteins, Exocytosis, Mice, Transgenic, Molecular Sequence Data, Nerve Tissue Proteins, Synaptic Transmission, Neurons, Neuropeptides, Synaptic Vesicles, Microscopy, Electron, Transmission, Mice
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