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A complex of the lipid transport ER proteins TMEM24 and C2CD2 with band 4.1 at cell-cell contacts
Open accessPreprint — published as 10.1083/jcb.202311137 · Paper page
Abstract
Junctions between the ER and the plasma membrane (ER/PM junctions) are implicated in calcium homeostasis, non-vesicular lipid transfer and other cellular functions. Two ER proteins that function both as membrane tethers to the PM via a polybasic motif in their C-terminus and as phospholipid transporters are brain-enriched TMEM24 (C2CD2L) and its paralog C2CD2. Based on an unbiased proximity ligation analysis, we found that both proteins can also form a complex with band 4.1 family members, which in turn can bind a variety of plasma membrane proteins including cell adhesion molecules such as SynCAM 1. This complex results in the enrichment of TMEM24 and C2CD2 containing ER/PM junctions at sites of cell contacts. Dynamic properties of TMEM24-dependent ER/PM contacts are impacted when in complex as TMEM24 present at cell adjacent junctions is not shed by calcium rise, unlike TMEM24 at non-cell adjacent junctions. These findings suggest that cell-contact interactions control ER/PM junctions via TMEM24 complexes involving band 4.1 proteins. SUMMARY: The ER-anchored lipid transfer proteins TMEM24/C2CD2L and its paralog C2CD2 mediate formation of ER-plasma membrane junctions at sites of cell-cell contacts by interacting with band 4.1 family members and indirectly with cell adhesion proteins.
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Metadata
- Authors
- Johnson, B., Iuliano, M., Lam, T., Biederer, T., & De Camilli, P.
- Affiliations
- Howard Hughes Medical Institute (US)
- Tufts University (US)
- Yale University (US)
- Venue
- The Journal of Cell Biology
- Publisher
- openRxiv
- Published
- 2023-12-06
- Volume
- 223
- Issue
- 11
- ISSN
- 0021-9525 (ISSN-L)
- PMC
- PMC11334333
- OpenAlex
- W4401700569
- Cited by
- 11
- References
- 1
- Citations by year
- 2026: 3 · 2025: 6 · 2024: 1 · 2023: 1
- FWCI
- 2.24
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- cc-by
- Locations
- The Journal of Cell Biology (publishedVersion, cc-by)
- bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- PubMed Central (submittedVersion, cc-by)
- Funders
- Yale University (S10OD019967, S10OD018034, S10OD02365101A1)
- National Institutes of Health (1s10od019967-01, S10OD02365101A1, 1s10od018034-01, NS36251, DA-018343, NS036251)
- Yale School of Medicine
- National Institute on Drug Abuse (R01DA018928, P30DA018343)
- National Institute of Neurological Disorders and Stroke (R01NS036251)
- Kavli Institute for Neuroscience, Yale School of Medicine
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular transport and secretion
- Life Sciences › Neuroscience › Sensory Systems › Ion Channels and Receptors
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Lipid Membrane Structure and Behavior
- Keywords
- band 4.1, ER-plasma membrane junctions, lipid transport, cell-cell contact, calcium homeostasis, protein complex formation, neurons
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