Synaptic Vesicle Size and Number Are Regulated by a Clathrin Adaptor Protein Required for Endocytosis
Open accessAbstract
Clathrin-mediated endocytosis is thought to involve the activity of the clathrin adaptor protein AP180. However, the role of this protein in endocytosis in vivo remains unknown. Here, we show that a mutation that eliminates an AP180 homolog (LAP) in Drosophila severely impairs the efficiency of synaptic vesicle endocytosis and alters the normal localization of clathrin in nerve terminals. Most importantly, the size of both synaptic vesicles and quanta is significantly increased in lap mutants. These results provide novel insights into the molecular mechanism of endocytosis and reveal a role for AP180 in regulating vesicle size through a clathrin-dependent reassembly process.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
PICALM has a role in clathrin-mediated endocytosis in non-MG cells.
“and the role of PICALM in clathrin-mediated endocytosis in non-MG cells31,32”
From PICALM Alzheimer’s risk allele causes aberrant lipid droplets in microglia (2025) · cites this paper as [32]
The Results passage on the Drosophila lap gene (page not provided) identifies LAP as an AP180-family protein with a human homolog, and the paper reports that loss of LAP impairs synaptic-vesicle endocytosis. It does not directly establish a role for human PICALM in clathrin-mediated endocytosis in non-MG cells; that part is an extrapolation from the homolog studied. (LLM, conf=0.82)
Experimental — accuracy not yet measured
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
No references could be resolved yet.
Research works printed but not linked: 2
- S.K. (1993). The Drosophila clathrin heavy chain gene: clathrin func- Katz, B. (1969). The release of neural transmitter substances, (Liv- tion is essential in a multicellular organism. Genetics 134, 1119- erpool, UK: Liverpool University Press). 1134.
- Sambrook, J., Fritsch, E.F., and Maniatis, T. (1989). Molecular Clon- ing: A Laboratory Manual, Second Edition. (Cold Spring Harbor, NY: Cold Spring Harbor Laboratory Press).
Cited by
Sorted by citations
Alzheimer’s Disease Risk Genes and Mechanisms of Disease Pathogenesis
Karch, C. M., & Goate, A. M. (2015) · Biological Psychiatry · doi:10.1016/j.biopsych.2014.05.006 · Cited by 1,357 · see citing works
Harrison, P. (2004) · Psychopharmacology · doi:10.1007/s00213-003-1761-y · Cited by 693 · see citing works
Kirchhausen, T. (2000) · Annual Review of Biochemistry · doi:10.1146/annurev.biochem.69.1.699 · Cited by 560 · see citing works
Saheki, Y., & De Camilli, P. (2012) · Cold Spring Harbor Perspectives in Biology · doi:10.1101/cshperspect.a005645 · Cited by 457 · see citing works
The Morphological and Molecular Nature of Synaptic Vesicle Priming at Presynaptic Active Zones
Imig, C., Min, S.-W., Krinner, S., Arancillo, M., Rosenmund, C., Südhof, T. C., Rhee, J., Brose, N., & Cooper, B. H. (2014) · Neuron · doi:10.1016/j.neuron.2014.10.009 · Cited by 389 · see citing works
Clathrin regenerates synaptic vesicles from endosomes
Watanabe, S., Trimbuch, T., Camacho-Pérez, M., Rost, B. R., Brokowski, B., Söhl-Kielczynski, B., Felies, A., Davis, M. W., Rosenmund, C., & Jorgensen, E. M. (2014) · Nature · doi:10.1038/nature13846 · Cited by 333 · see citing works
Molecular Circuitry of Endocytosis at Nerve Terminals
Dittman, J., & Ryan, T. A. (2009) · Annual Review of Cell and Developmental Biology · doi:10.1146/annurev.cellbio.042308.113302 · Cited by 238 · see citing works
Miller, S. E., Mathiasen, S., Bright, N. A., Pierre, F., Kelly, B. T., Kladt, N., Schauss, A., Merrifield, C. J., Stamou, D., Höning, S., et al. (2015) · Developmental Cell · doi:10.1016/j.devcel.2015.03.002 · Cited by 207 · see citing works
Xiao, Q., Gil, S.-C., Yan, P., Wang, Y., Han, S., Gonzales, E., Perez, R., Cirrito, J. R., & Lee, J.-M. (2012) · Journal of Biological Chemistry · doi:10.1074/jbc.m111.338376 · Cited by 166 · see citing works
Fate of micelles and quantum dots in cells
Maysinger, D., Lovrić, J., Eisenberg, A., & Savić, R. (2007) · European Journal of Pharmaceutics and Biopharmaceutics · doi:10.1016/j.ejpb.2006.08.011 · Cited by 160 · see citing works
Networks of Neuronal Genes Affected by Common and Rare Variants in Autism Spectrum Disorders
Ben-David, E., & Shifman, S. (2012) · PLoS Genetics · doi:10.1371/journal.pgen.1002556 · Cited by 145 · see citing works
Visualizing presynaptic function
Kavalali, E. T., & Jorgensen, E. M. (2014) · Nature Neuroscience · doi:10.1038/nn.3578 · Cited by 126 · see citing works
Isoflurane inhibits the neurotransmitter release machinery
Herring, B. E., Xie, Z., Marks, J., & Fox, A. P. (2009) · Journal of Neurophysiology · doi:10.1152/jn.00252.2009 · Cited by 83 · see citing works
Scaling of Subcellular Structures
Marshall, W. F. (2020) · Annual Review of Cell and Developmental Biology · doi:10.1146/annurev-cellbio-020520-113246 · Cited by 54 · see citing works
PICALM Alzheimer’s risk allele causes aberrant lipid droplets in microglia
Kozlova, A., Zhang, S., Sudwarts, A., Zhang, H., Smirnou, S., Byeon, S. K., Thapa, C., Sun, X., Stephenson, K., Zhao, X., et al. (2025) · Nature · doi:10.1038/s41586-025-09486-x · Cited by 53 · see citing works
“Considering the importance of MG phagocytosis in AD 29,30 and the role of PICALM in clathrin-mediated endocytosis in non-MG cells 31,32 , we hypothesized that the LOAD-risk allele of rs10792832 influences iMG phagocytosis by reducing PICALM expression.”
Self-citationOjelade, S. A., Lee, T. V., Giagtzoglou, N., Yu, L., Ugur, B., Li, Y., Duraine, L., Zuo, Z., Petyuk, V., De Jager, P. L., et al. (2019) · Cell Reports · doi:10.1016/j.celrep.2019.07.041 · Cited by 42 · see citing works
Self-citationSynapsEM: Computer-Assisted Synapse Morphometry
Watanabe, S., Davis, M. W., Kusick, G. F., Iwasa, J., & Jorgensen, E. M. (2020) · Frontiers in Synaptic Neuroscience · doi:10.3389/fnsyn.2020.584549 · Cited by 34 · see citing works
Modulation of PICALM Levels Perturbs Cellular Cholesterol Homeostasis
Mercer, J. L., Argus, J. P., Crabtree, D. M., Keenan, M. M., Wilks, M. Q., Chi, J.-T. A., Bensinger, S. J., Lavau, C. P., & Wechsler, D. S. (2015) · PLOS ONE · doi:10.1371/journal.pone.0129776 · Cited by 17 · see citing works
Small, C., Harper, C., Jiang, A., Kontaxi, C., Yak, N., Malapaka, A., Davenport, E. C., Wallis, T. P., Gormal, R. S., Joensuu, M., et al. (2022) · doi:10.1101/2022.12.12.520075 · Cited by 4 · see citing works
- Authors
- Zhang, B., Koh, Y. H., Beckstead, R. B., Budnik, V., Ganetzky, B., & Bellen, H. J.
- Affiliations
- Howard Hughes Medical Institute (US)
- University of Massachusetts Amherst (US)
- University of Wisconsin–Madison (US)
- Corresponding author
- Bellen, Hugo J
- Venue
- Neuron
- Publisher
- Elsevier BV
- Published
- 1998-12
- Volume
- 21
- Issue
- 6
- Pages
- 1465-1475
- ISSN
- 0896-6273 (ISSN-L)
- OpenAlex
- W2068437038
- Cited by
- 434
- References
- 0
- Citations by year
- 2026: 4 · 2025: 10 · 2024: 9 · 2023: 7 · 2022: 11 · 2021: 17 · 2020: 15 · 2019: 13 · 2018: 15 · 2017: 9 · 2016: 15 · 2015: 17 · 2014: 18 · 2013: 20 · 2012: 17
- FWCI
- 6.75
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Neuron (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health
- 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 › Extracellular vesicles in disease
- Keywords
- clathrin-mediated endocytosis, AP180, clathrin adaptor proteins, synaptic vesicle endocytosis, presynaptic terminals, Drosophila
- MeSH terms
- Amino Acid Sequence, Animals, Axons, DNA-Binding Proteins, Drosophila, Embryo, Nonmammalian, Endocytosis, Molecular Sequence Data, Nerve Endings, Nerve Tissue Proteins, Nuclear Proteins, Phosphoproteins, Synaptic Vesicles, Gene Library, Sequence Alignment, Gene Expression Regulation, Developmental, CCAAT-Enhancer-Binding Proteins, Adaptor Proteins, Vesicular Transport, Monomeric Clathrin Assembly Proteins
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review