PreprintCited by 11Cellular transport and secretionIon Channels and ReceptorsLipid Membrane Structure and Behavior

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A complex of the lipid transport ER proteins TMEM24 and C2CD2 with band 4.1 at cell-cell contacts

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Johnson, Ben, Iuliano, Maria, Lam, TuKiet, Biederer, Thomas, De Camilli, Pietro·2023·The Journal of Cell Biology

Preprint — 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)
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
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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