Evidence map›Paper›PMID 35740256›Full record

ReviewBiomedicines2022

KDEL Receptors: Pathophysiological Functions, Therapeutic Options, and Biotechnological Opportunities.

Ilaria Cela, Beatrice Dufrusine, Claudia Rossi, Alberto Luini, Vincenzo De Laurenzi, Luca Federici, Michele Sallese

Open access · goldAbstract readReview
In one paragraph

Review in Biomedicines, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.

0numbers the graph read from it
0cells of the map it votes in
19citing papers in PubMed
2.6field-weighted citation impact, top 10% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

19 citing papers in PubMed, 26 citations in OpenAlex.

  1. Article
  2. Review
  3. Article
  4. Article
  5. Review
  6. Article
  7. Review
  8. Review
  9. Article
  10. Article
  11. Article
  12. Solute Carrier Family 26 Member 4 (SLC26A4), A Potential Therapeutic Target for Asthma.Journal of respiratory biology and translational medicine · 2024
    Article
  13. Article
  14. Article
  15. Ion channel trafficking implications in heart failure.Frontiers in cardiovascular medicine · 2024
    Review
  16. Unfolded protein responses in T cell immunity.Frontiers in immunology · 2024
    Review
  17. Article
  18. Review
  19. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

7 authors at 2 institutions in 1 country.

Ilaria CelaDepartment of Innovative Technologies in Medicine and Dentistry, "G. D'Annunzio" University of Chieti-Pescara, 66100 Chieti, Italy.
Beatrice DufrusineDepartment of Innovative Technologies in Medicine and Dentistry, "G. D'Annunzio" University of Chieti-Pescara, 66100 Chieti, Italy.ORCID 0000-0001-7515-9794
Claudia RossiCenter for Advanced Studies and Technology (CAST), "G. D'Annunzio" University of Chieti-Pescara, 66100 Chieti, Italy.ORCID 0000-0003-0949-0280
Alberto LuiniInstitute for Experimental Endocrinology and Oncology "Gaetano Salvatore" (IEOS)-Branch Office, Via Pietro Castellino 111, 80131 Napoli, Italy.
Vincenzo De LaurenziDepartment of Innovative Technologies in Medicine and Dentistry, "G. D'Annunzio" University of Chieti-Pescara, 66100 Chieti, Italy.
Luca FedericiDepartment of Innovative Technologies in Medicine and Dentistry, "G. D'Annunzio" University of Chieti-Pescara, 66100 Chieti, Italy.ORCID 0000-0002-9366-4492
Michele SalleseDepartment of Innovative Technologies in Medicine and Dentistry, "G. D'Annunzio" University of Chieti-Pescara, 66100 Chieti, Italy.ORCID 0000-0002-2555-3571
University of Chieti-Pescara · ITInstitute for Experimental Endocrinology and Oncology · IT

Funding

Telethon Foundation GGP20092
6 · The paper itself

Abstract

KDEL receptors (KDELRs) are ubiquitous seven-transmembrane domain proteins encoded by three mammalian genes. They bind to and retro-transport endoplasmic reticulum (ER)-resident proteins with a C-terminal Lys-Asp-Glu-Leu (KDEL) sequence or variants thereof. In doing this, KDELR participates in the ER quality control of newly synthesized proteins and the unfolded protein response. The binding of KDEL proteins to KDELR initiates signaling cascades involving three alpha subunits of heterotrimeric G proteins, Src family kinases, protein kinases A (PKAs), and mitogen-activated protein kinases (MAPKs). These signaling pathways coordinate membrane trafficking flows between secretory compartments and control the degradation of the extracellular matrix (ECM), an important step in cancer progression. Considering the basic cellular functions performed by KDELRs, their association with various diseases is not surprising. KDELR mutants unable to bind the collagen-specific chaperon heat-shock protein 47 (HSP47) cause the osteogenesis imperfecta. Moreover, the overexpression of KDELRs appears to be linked to neurodegenerative diseases that share pathological ER-stress and activation of the unfolded protein response (UPR). Even immune function requires a functional KDELR1, as its mutants reduce the number of T lymphocytes and impair antiviral immunity. Several studies have also brought to light the exploitation of the shuttle activity of KDELR during the intoxication and maturation/exit of viral particles. Based on the above, KDELRs can be considered potential targets for the development of novel therapeutic strategies for a variety of diseases involving proteostasis disruption, cancer progression, and infectious disease. However, no drugs targeting KDELR functions are available to date; rather, KDELR has been leveraged to deliver drugs efficiently into cells or improve antigen presentation.

Indexed as

chaperones retrievalendoplasmic reticulum homeostasistargeted therapiesunfolded protein responseviruses trafficking

Identifiers

PMID35740256
PMCPMC9220330
OpenAlexW4281570882

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.