The Clathrin Adaptor AP-1A Mediates Basolateral Polarity
Open accessAbstract
Clathrin and the epithelial-specific clathrin adaptor AP-1B mediate basolateral trafficking in epithelia. However, several epithelia lack AP-1B, and mice knocked out for AP-1B are viable, suggesting the existence of additional mechanisms that control basolateral polarity. Here, we demonstrate a distinct role of the ubiquitous clathrin adaptor AP-1A in basolateral protein sorting. Knockdown of AP-1A causes missorting of basolateral proteins in MDCK cells, but only after knockdown of AP-1B, suggesting that AP-1B can compensate for lack of AP-1A. AP-1A localizes predominantly to the TGN, and its knockdown promotes spillover of basolateral proteins into common recycling endosomes, the site of function of AP-1B, suggesting complementary roles of both adaptors in basolateral sorting. Yeast two-hybrid assays detect interactions between the basolateral signal of transferrin receptor and the medium subunits of both AP-1A and AP-1B. The basolateral sorting function of AP-1A reported here establishes AP-1 as a major regulator of epithelial 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 Gravotta et al., 2012
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Clathrin adaptor AP1B controls adenovirus infectivity of epithelial cells
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- Authors
- Gravotta, D., Carvajal-Gonzalez, J. M., Mattera, R., Deborde, S., Banfelder, J. R., Bonifacino, J. S., & Rodriguez-Boulan, E.
- Affiliations
- Weill Cornell Medicine (US)
- National Institutes of Health (US)
- Corresponding author
- Gravotta, Diego
- Rodriguez-Boulan, Enrique
- Venue
- Developmental Cell
- Publisher
- Elsevier BV
- Published
- 2012-04
- Volume
- 22
- Issue
- 4
- Pages
- 811-823
- ISSN
- 1534-5807 (ISSN-L)
- PMC
- PMC3690600
- OpenAlex
- W2099195160
- Cited by
- 148
- References
- 1
- Citations by year
- 2026: 2 · 2025: 2 · 2024: 3 · 2023: 4 · 2022: 13 · 2021: 9 · 2020: 9 · 2019: 9 · 2018: 2 · 2017: 6 · 2016: 13 · 2015: 17 · 2014: 19 · 2013: 24 · 2012: 16
- FWCI
- 10.72
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Developmental Cell (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- Research to Prevent Blindness
- Dyson Foundation
- National Institutes of Health
- National Heart, Lung, and Blood Institute
- National Eye Institute (EY08538, R01EY008538)
- National Institute of General Medical Sciences (GM34108, R01GM034107)
- National Institute of Child Health and Human Development
- Eunice Kennedy Shriver National Institute of Child Health and Human Development
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular transport and secretion
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Ion Transport and Channel Regulation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Developmental Biology and Gene Regulation
- Keywords
- epithelial polarity, trans-Golgi network, recycling endosomes, transferrin receptor, MDCK cells
- MeSH terms
- Animals, Cell Membrane, Cells, Cultured, Clathrin, Dogs, Epithelial Cells, Fluorescent Antibody Technique, Receptors, LDL, Receptors, Transferrin, Endosomes, Cell Polarity, Two-Hybrid System Techniques, Protein Transport, trans-Golgi Network, Adaptor Protein Complex 1, RNA, Small Interfering
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