AI Article Synopsis
- Scientists studied a rare blood condition called paroxysmal nocturnal hemoglobinuria (PNH) to find out what caused it without finding usual mutations in the PIGA gene.
- They found a change in the PIGT gene and a big deletion in white blood cells, which affected how GPI anchors attached to proteins.
- The research showed that even if GPI anchors are fully made, problems with how they connect to proteins can still cause PNH.
Article Abstract
To ascertain the genetic basis of a paroxysmal nocturnal hemoglobinuria (PNH) case without somatic mutations in PIGA, we performed deep next-generation sequencing on all exons of known genes of the glycosylphosphatidylinositol (GPI) anchor synthesis pathway. We identified a heterozygous germline splice site mutation in PIGT and a somatic 8-MB deletion in granulocytes affecting the other copy of PIGT. PIGA is essential for GPI anchor synthesis, whereas PIGT is essential for attachment of the preassembled GPI anchor to proteins. Although a single mutation event in the X-chromosomal gene PIGA is known to cause GPI-anchored protein deficiency, 2 such hits are required in the autosomal gene PIGT. Our data indicate that PNH can occur even in the presence of fully assembled GPI if its transfer to proteins is defective in hematopoietic stem cells.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1182/blood-2013-01-481499 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Regulation of autophagy by protein lipidation.
Adv Biotechnol (Singap)
September 2024
Department of Neurosurgery, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, 610041, China.
Autophagy is a conserved catabolic recycling pathway that can eliminate cytosolic materials to maintain homeostasis and organelle functions. Many studies over the past few decades have demonstrated that abnormal autophagy is associated with a variety of diseases. Protein lipidation plays an important role in the regulation of autophagy by affecting protein trafficking, localization, stability, interactions and signal transduction.
View Article and Find Full Text PDFThe road of lipid migration in flaxseed (Linum usitatissimum L.) during germination.
Food Res Int
February 2025
Research Center of Grain and Oil Functionalized Processing in Universities of Shaanxi Province, College of Food Science and Engineering, Northwest A&F University, 22 Xinong Road, Yangling 712100, Shaanxi, PR China. Electronic address:
Lipids are essential sources of carbon and energy during flaxseed germination; however, the dynamic changes in key lipid metabolites, pathways, and their locations remain unclear. This study revealed that oil bodies migrated from well-distributed locations to the cell wall between 0-2 d, with cell contours gradually blurring during 2-3 d, initiating the germination process. Subsequently, the order of oil body migration was leaf > stem > root during 4-7 d.
View Article and Find Full Text PDFUnlocking the signaling potential of GPI-anchored proteins through lipolytic cleavage.
Trends Cell Biol
January 2025
Division of Biochemistry, The Netherlands Cancer Institute, Amsterdam, The Netherlands. Electronic address:
Glycosylphosphatidylinositol (GPI)-anchored proteins (APs) regulate numerous biological processes through interaction with signaling effectors at the cell surface. As a unique feature, GPI-APs can be released from their anchors by multi-pass GPI-specific phospholipases (types A2, C, and D) to impact signaling networks, phenotype, and cell fate; however, many questions remain outstanding. Here, we discuss and expand our current understanding of the distinct GPI-specific phospholipases, their substrates, effector pathways, and emerging physiological roles, with a focus on the six-transmembrane ecto-phospholipases GDE2 (GDPD5) and GDE3 (GDPD2).
View Article and Find Full Text PDFA novel transgenic reporter of extracellular acidification in zebrafish elucidates skeletal muscle T-tubule pH regulation.
Dev Dyn
January 2025
Department of Medicine, Michigan State University College of Human Medicine, East Lansing, Michigan, USA.
Disruption of extracellular pH and proton-sensing can profoundly impact cellular and protein functions, leading to developmental defects. To visualize changes in extracellular pH in the developing embryo, we generated a zebrafish transgenic line that ubiquitously expresses the ratiometric pH-sensitive fluorescent protein pHluorin2, tethered to the extracellular face of the plasma membrane using a glycosylphosphatidylinositol (GPI) anchor. Monitoring of pHluorin2 with ratiometric fluorescence revealed dynamic and discrete domains of extracellular acidification over the first 72 h of embryonic development.
View Article and Find Full Text PDFSynthesis of Glycosylphosphatidylinositol Analogues with an Unnatural -D-Glucosamine-(1→6)--Inositol Motif.
J Carbohydr Chem
April 2024
Department of Chemistry, University of Florida, 214 Leigh Hall, Gainesville, FL 32611, USA.
Glycosylphosphatidylinositol (GPI) anchors contain a unique α-D-glucosamine-(1→6)--inositol [αGlcN(1,6)Ins] motif in their conserved core structure. To facilitate investigations of the functional roles of this structural motif, two GPI analogues containing unnatural βGlcN(1,6)Ins, instead of αGlcN(1,6)Ins, and an alkyne group at different positions of the GPI core were designed and synthesized. To this end, an orthogonally protected pseudopentasaccharide derivative of GPIs with the βGlcN(1,6)Ins motif was convergently constructed via [3+2] glycosylation and used as the common intermediate to prepare both GPI analogues by streamlined synthetic protocols.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!