Architecture and dynamics of a novel desmosome-endoplasmic reticulum organelle

Bharathan, Navaneetha Krishnan; Giang, W.; Aaron, Jesse; Khuon, Satya; Chew, Teng‐Leong; Preibisch, Stephan; Trautman, Eric T.; Heinrich, Larissa; Bogovic, John A.; Bennett, Davis; Ackerman, David G.; Park, Woo-Hyun; Petruncio, Alyson; Weigel, Aubrey V.; Saalfeld, Stephan; Vogl, A. Wayne; Stahley, Sara N.; Kowalczyk, Andrew P.

doi:10.1101/2022.07.07.499185

Cited by 6 publications

(5 citation statements)

References 43 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Most recently, epidermal keratins were identified in close association with peripheral ER compartments at desmosomes, where they are crucial to maintaining desmosomeassociated ER compartments, as seen by the disruption of ER-desmosome complexes upon the expression of a disease-associated KRT14 mutation [40]. Based on parallel staining of GPR115 and the ER markers RTN4 and CKAP4 in HaCaT keratinocytes, it appears unlikely that the GPR115 species that localize close to KRT1/10 reside in an ER compartment.…”

Section: Discussionmentioning

confidence: 99%

The Adhesion G-Protein-Coupled Receptor GPR115/ADGRF4 Regulates Epidermal Differentiation and Associates with Cytoskeletal KRT1

Winkler

Quaas

Glasmacher

et al. 2022

Cells

View full text Add to dashboard Cite

Among the 33 human adhesion G-protein-coupled receptors (aGPCRs), a unique subfamily of GPCRs, only ADGRF4, encoding GPR115, shows an obvious skin-dominated transcriptomic profile, but its expression and function in skin is largely unknown. Here, we report that GPR115 is present in a small subset of basal and in most suprabasal, noncornified keratinocytes of the stratified epidermis, supporting epidermal transcriptomic data. In psoriatic skin, characterized by hyperproliferation and delayed differentiation, the expression of GPR115 and KRT1/10, the fundamental suprabasal keratin dimer, is delayed. The deletion of ADGRF4 in HaCaT keratinocytes grown in an organotypic mode abrogates KRT1 and reduces keratinocyte stratification, indicating a role of GPR115 in epidermal differentiation. Unexpectedly, endogenous GPR115, which is not glycosylated and is likely not proteolytically processed, localizes intracellularly along KRT1/10-positive keratin filaments in a regular pattern. Our data demonstrate a hitherto unknown function of GPR115 in the regulation of epidermal differentiation and KRT1.

show abstract

Section: Discussionmentioning

confidence: 99%

The Adhesion G-Protein-Coupled Receptor GPR115/ADGRF4 Regulates Epidermal Differentiation and Associates with Cytoskeletal KRT1

Winkler

Quaas

Glasmacher

et al. 2022

Cells

View full text Add to dashboard Cite

show abstract

“…To experimentally determine whether palmitoylation drives DSG1 raft association, we stably expressed DSG1 PALM -GFP in DSG-null A431 cells. A431 cells are an immortal human carcinoma cell line commonly used to assess desmosome assembly and function (Godsel et al, 2005; Brennan et al, 2012; Baddam et al, 2018; Bharathan et al, 2023). DSG2 is the prevalent DSG isoform expressed in A431 cells (Schäfer et al, 1994, Zimmer et al, 2022).…”

Section: Resultsmentioning

confidence: 99%

The transmembrane domain of the desmosomal cadherin desmoglein-1 governs lipid raft association to promote desmosome adhesive strength

Zimmer,

Giang,

Levental

et al. 2024

Preprint

Self Cite

View full text Add to dashboard Cite

Cholesterol- and sphingolipid-enriched domains called lipid rafts are hypothesized to selectively coordinate protein complex assembly within the plasma membrane to regulate cellular functions. Desmosomes are mechanically resilient adhesive junctions that associate with lipid raft membrane domains, yet the mechanisms directing raft association of the desmosomal proteins, particularly the transmembrane desmosomal cadherins, are poorly understood. We identified the desmoglein-1 (DSG1) transmembrane domain (TMD) as a key determinant of desmoglein lipid raft association and designed a panel of DSG1TMD variants to assess the contribution of TMD physicochemical properties (length, bulkiness, and palmitoylation) to DSG1 lipid raft association. Sucrose gradient fractionations revealed that TMD length and bulkiness, but not palmitoylation, govern DSG1 lipid raft association. Further, DSG1 raft association determines plakoglobin recruitment to raft domains. Super-resolution imaging and functional assays uncovered a strong relationship between the efficiency of DSG1TMD lipid raft association and the formation of morphologically and functionally robust desmosomes. Lipid raft association regulated both desmosome assembly dynamics and DSG1 cell surface stability, indicating that DSG1 lipid raft association is required for both desmosome formation and maintenance. These studies identify the biophysical properties of desmoglein transmembrane domains as key determinants of lipid raft association and desmosome adhesive function.

show abstract

“…Interestingly, TMEM24 was previously found as a potential interactor of 4.1R using a rat kidney yeast two-hybrid screen (Calinisan et al, 2005), although this interaction was not further validated. We note that the list of 36 significant hits includes desmoglien-2 (DSG-2), a protein that was recently shown to be part of symmetrical desmosome-endoplasmic reticulum subcellular complexes at cell-cell contacts (Bharathan et al, 2023).…”

Section: Resultsmentioning

confidence: 99%

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

Johnson,

Iuliano,

Lam

et al. 2023

Preprint

View full text Add to dashboard Cite

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.SUMMARYThe 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.

show abstract

Architecture and dynamics of a novel desmosome-endoplasmic reticulum organelle

Cited by 6 publications

References 43 publications

The Adhesion G-Protein-Coupled Receptor GPR115/ADGRF4 Regulates Epidermal Differentiation and Associates with Cytoskeletal KRT1

The Adhesion G-Protein-Coupled Receptor GPR115/ADGRF4 Regulates Epidermal Differentiation and Associates with Cytoskeletal KRT1

The transmembrane domain of the desmosomal cadherin desmoglein-1 governs lipid raft association to promote desmosome adhesive strength

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

Contact Info

Product

Resources

About