In 1999, Goodpasture antigen-binding protein (GPBP) was identified as a protein interacting with the N-terminal region of the human Goodpasture antigen, linked to collagen IV in patients with Goodpasture syndrome, an autoimmune disease. In 2003, a splice variant lacking a serine-rich domain was discovered, which is involved in the cytosolic transport of ceramide, leading to its renaming as Ceramide Transfer Protein (CERT). This dual functionality has sparked debate regarding the roles of GPBP/CERT, as they appear to participate in distinct research fields and are implicated in various pathologies. This review follows the guidelines of the Preferred Reporting Items for Systematic Reviews (PRISMA). It compiles data from searches on Medline (PubMed) and Web of Science conducted between February and November 2022. Out of 465 records, 47 publications were selected for review. The literature predominantly focuses on GPBP/CERT as ceramide transporters. Notably, no studies contradict either hypothesis, with substantial scientific evidence supporting both roles. The need for further research is clear, and new insights into these proteins' involvement in multiple pathologies could drive future therapeutic strategies. GPBP and CERT are multifunctional proteins with roles beyond collagen organization and ceramide transport, extending to autoimmune disorders, neurodegenerative diseases, and cancer. The ongoing controversy highlights the necessity for continued investigation, which promises to offer significant insights and potential therapeutic avenues.
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http://dx.doi.org/10.3390/ijms252313179 | DOI Listing |
Int J Mol Sci
December 2024
Molecular and Mitochondrial Medicine Research Group, School of Medicine and Health Sciences, Catholic University of Valencia San Vicente Mártir, C/Quevedo no. 2, 46001 Valencia, Spain.
In 1999, Goodpasture antigen-binding protein (GPBP) was identified as a protein interacting with the N-terminal region of the human Goodpasture antigen, linked to collagen IV in patients with Goodpasture syndrome, an autoimmune disease. In 2003, a splice variant lacking a serine-rich domain was discovered, which is involved in the cytosolic transport of ceramide, leading to its renaming as Ceramide Transfer Protein (CERT). This dual functionality has sparked debate regarding the roles of GPBP/CERT, as they appear to participate in distinct research fields and are implicated in various pathologies.
View Article and Find Full Text PDFBioorg Med Chem
March 2017
SPCMIB, UMR5068 CNRS-Université Paul Sabatier-Toulouse III, 118 route de Narbonne, Toulouse F-31062, France. Electronic address:
The enigmatical dichotomy between the two CERT/GPBP protein isoforms, their vast panel of biological implications and the scarcity of known antagonist series call for new ligand chemotypes identification. We report the design of iminosugar-based ceramide mimics for the development of new START domain ligands potentially targeting either protein isoforms. Strategic choice of (i) an iminoxylitol core structure and (ii) the positioning of two dodecyl residues led to an extent of protein binding comparable to that of the natural cargo lipid ceramide or the archetypical inhibitor HPA-12.
View Article and Find Full Text PDFBiochim Biophys Acta
May 2014
Department of Biochemistry and Cell Biology, National Institute of Infectious Diseases, 1-23-1, Toyama, Shinjuku-ku, Tokyo 162-8640, Japan. Electronic address:
Life creates many varieties of lipids. The choline-containing sphingophospholipid sphingomyelin (SM) exists ubiquitously or widely in vertebrates and lower animals, but is absent or rare in bacteria, fungi, protists, and plants. In the biosynthesis of SM, ceramide, which is synthesized in the endoplasmic reticulum, is transported to the Golgi region by the ceramide transport protein CERT, probably in a non-vesicular manner, and is then converted to SM by SM synthase, which catalyzes the reaction of phosphocholine transfer from phosphatidylcholine (PtdCho) to ceramide.
View Article and Find Full Text PDFNeurosci Lett
January 2012
Department of Neuroscience, Faculty of Health, Medicine and Life Sciences, Maastricht University, Maastricht, The Netherlands.
Ceramides are lipids that are abundant in brain tissue where they have an important structural role in cellular membranes. Ceramides are also powerful intracellular signalling molecules controlling cell death, growth and differentiation. So far, the ceramide transfer protein (CERT), a shorter splice variant of the Goodpasture antigen-binding protein (GPBP), is the only known protein with the ability to shuttle ceramide from the endoplasmic reticulum to the Golgi apparatus.
View Article and Find Full Text PDFJ Neurochem
June 2010
Department of Neuroscience, School for Mental Health and Neuroscience, Faculty of Health, Medicine and Life Sciences, Maastricht University, Maastricht, The Netherlands.
The Goodpasture antigen-binding protein (GPBP) and its splice variant the ceramide transporter (CERT) are multifunctional proteins that have been found to play important roles in brain development and biology. However, the function of GPBP and CERT is controversial because of their involvement in two apparently unrelated research fields: GPBP was initially isolated as a protein associated with collagen IV in patients with the autoimmune disease Goodpasture syndrome. Subsequently, a splice variant lacking a serine-rich domain of 26 amino acids (GPBPDelta26) was found to mediate the cytosolic transport of ceramide and was therefore (re)named CERT.
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