Evidence for CALM in Directing VAMP2 Trafficking
Open accessAbstract
Clathrin assembly lymphoid myeloid leukemia protein (CALM) is a clathrin assembly protein with a domain structure similar to the neuron‐specific assembly protein AP180. We have previously found that CALM is expressed in neurons and present in synapses. We now report that CALM has a neuron‐related function: it facilitates the endocytosis of the synaptic vesicle protein VAMP2 from the plasma membrane. Overexpression of CALM leads to the reduction of cell surface VAMP2, whereas knockdown of CALM by RNA interference results in the accumulation of surface VAMP2. The AP180 N‐terminal homology (ANTH) domain of CALM is required for its effect on VAMP2 trafficking, and the ANTH domain itself acts as a dominant‐negative mutant. Thus, our results reveal a role for CALM in directing VAMP2 trafficking during endocytosis.
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AD brains show reduced synapse number and synaptic density correlates with cognitive defects better than plaques and tangles.
“AD brains show a reduced number of synapses and stereological and biochemical analysis has shown that this reduction in synaptic density correlates with cognitive defects better than the accumulation of plaques and tangles40.”
From Genome-wide association study identifies variants at CLU and PICALM associated with Alzheimer's disease (2009) · cites this paper as [40]
The paper’s Abstract and Discussion address CALM’s role in VAMP2 trafficking, not synapse loss in Alzheimer’s disease. Searches for Alzheimer’s disease, synaptic density, cognitive impairment, plaques, and tangles found no passage in our copy supporting the claimed comparison. (LLM, conf=0.76)
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- Authors
- Harel, A., Wu, F., Mattson, M. P., Morris, C. M., & Yao, P. J.
- Affiliations
- National Institute on Aging (US)
- Corresponding author
- Yao, Pamela J.
- Venue
- Traffic
- Publisher
- Wiley
- Published
- 2007-12-21
- Volume
- 9
- Issue
- 3
- Pages
- 417-429
- ISSN
- 1398-9219 (ISSN-L)
- 1600-0854
- OpenAlex
- W2025913180
- Cited by
- 144
- References
- 1
- Citations by year
- 2026: 2 · 2025: 1 · 2024: 3 · 2023: 3 · 2022: 4 · 2021: 3 · 2020: 7 · 2019: 5 · 2018: 4 · 2017: 6 · 2016: 11 · 2015: 7 · 2014: 14 · 2013: 10 · 2012: 17
- FWCI
- 3.86
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Traffic (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
- Health Sciences › Medicine › Epidemiology › Autophagy in Disease and Therapy
- Keywords
- CALM, VAMP2, synaptic vesicle proteins, endocytosis, protein trafficking, clathrin assembly, AP180, dominant-negative mutant, synapses, neurons
- MeSH terms
- Animals, Cell Line, Cell Membrane, Endocytosis, Humans, Recombinant Proteins, Transfection, Transferrin, Mutagenesis, Site-Directed, PC12 Cells, Protein Structure, Tertiary, Protein Transport, Monomeric Clathrin Assembly Proteins, RNA Interference, RNA, Small Interfering, Vesicle-Associated Membrane Protein 2, Rats
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