Signal-mediated, AP-1/clathrin-dependent sorting of transmembrane receptors to the somatodendritic domain of hippocampal neurons
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Plasma membranes of the somatodendritic and axonal domains of neurons are known to have different protein compositions, but the molecular mechanisms that determine this polarized protein distribution remain poorly understood. Herein we show that somatodendritic sorting of various transmembrane receptors in rat hippocampal neurons is mediated by recognition of signals within the cytosolic domains of the proteins by the μ1A subunit of the adaptor protein-1 (AP-1) complex. This complex, in conjunction with clathrin, functions in the neuronal soma to exclude somatodendritic proteins from axonal transport carriers. Perturbation of this process affects dendritic spine morphology and decreases the number of synapses. These findings highlight the primary recognition event that underlies somatodendritic sorting and contribute to the evolving view of AP-1 as a global regulator of cell polarity.
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AP-1 is required for trafficking of transferrin receptor (TfR) to the basolateral PM in polarized MDCK cells and to the somatodendritic PM in rat hippocampal neurons.
“AP-1 has been shown to be required for the trafficking of transferrin receptor (TfR) to the basolateral PM in polarized Madin–Darby canine kidney (MDCK) epithelial cells (Gravotta et al., 2012) and the trafficking of TfR to the somatodendritic PM in rat hippocampal neurons (Farias et al., 2012).”
From Distinct anterograde trafficking pathways of BACE1 and amyloid precursor protein from the TGN and the regulation of amyloid-β production (2020) · cites this paper as Farias et al., 2012
The AP1 complex functions in intracellular transport of cargo proteins between the trans-Golgi apparatus and endosomes by linking clathrin to cargo proteins during vesicle membrane formation, and is important for somatodendritic transport of proteins required for neuronal polarity.
“The AP1 complex functions in the intracellular transport of cargo proteins between the trans-Golgi apparatus and endosomes by linking clathrin to the cargo proteins during vesicle membrane formation (Kirchhausen, 2000), and is important for the somatodendritic transport of proteins required for neuronal polarity (Farias et al., 2012).”
From A Highly Conserved Program of Neuronal Microexons Is Misregulated in Autistic Brains (2014) · cites this paper as Farias et al., 2012
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References 63 · Cited by 122
- Authors
- Farías, G. G., Cuitino, L., Guo, X., Ren, X., Jarnik, M., Mattera, R., & Bonifacino, J. S.
- Affiliations
- National Institutes of Health (US)
- Corresponding author
- Bonifacino, Juan S.
- Venue
- Neuron
- Publisher
- Elsevier BV
- Published
- 2012-09
- Volume
- 75
- Issue
- 5
- Pages
- 810-823
- ISSN
- 0896-6273 (ISSN-L)
- PMC
- PMC3439821
- OpenAlex
- W2009470502
- Cited by
- 122
- References
- 63
- Citations by year
- 2026: 4 · 2025: 4 · 2024: 16 · 2023: 10 · 2022: 5 · 2021: 5 · 2020: 7 · 2019: 11 · 2018: 7 · 2017: 3 · 2016: 12 · 2015: 14 · 2014: 14 · 2013: 9 · 2012: 1
- FWCI
- 5.75
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Neuron (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health (ZIA-HD001607)
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (ZIAHD001607)
- 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 › Physiology › Alzheimer's disease research and treatments
- Keywords
- transmembrane receptors, AP-1 complex, clathrin, neuronal polarity, axonal transport, dendritic spine morphology, synapse number, hippocampal neurons
- MeSH terms
- Amino Acid Sequence, Animals, Clathrin, Dendritic Cells, Hippocampus, Humans, Molecular Sequence Data, Neurons, Receptors, Cell Surface, Signal Transduction, Cell Polarity, Rats, Sprague-Dawley, Transgenes, Adaptor Protein Complex 1, Adaptor Protein Complex mu Subunits, Rats, Primary Cell Culture
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