Dysferlin and other non-red cell proteins accumulate in the red cell membrane of Diamond-Blackfan Anemia patients

Diamond Blackfan Anemia (DBA) is a congenital anemia usually caused by diverse mutations in ribosomal proteins. Although the genetics of DBA are well characterized, the mechanisms that lead to macrocytic anemia remain unclear. We systematically analyzed the proteomes of red blood cell membranes from...

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Bibliographic Details
Published in:PloS one 2014-01, Vol.9 (1), p.e85504-e85504
Main Authors: Pesciotta, Esther N, Sriswasdi, Sira, Tang, Hsin-Yao, Speicher, David W, Mason, Philip J, Bessler, Monica
Format: Article
Language:English
Subjects:
Abnormalities
Adenosine
Adolescent
Adult
Analysis
Anemia
Anemia, Diamond-Blackfan - blood
Anemia, Diamond-Blackfan - metabolism
Biology
Biosynthesis
Blood
Bone marrow
Cell adhesion & migration
Cell cycle
Cell membranes
Chemistry
Child
Child, Preschool
Diamonds
Dysferlin
Erythrocyte Membrane - metabolism
Erythrocytes
Erythropoiesis
Female
Fetuses
Gene expression
Gene mutation
Genetics
Genomics
Hemoglobin
Hemoglobins
Humans
Lupus
Major histocompatibility complex
Male
Medicine
Membrane proteins
Membrane Proteins - metabolism
Membranes
Muscle Proteins - metabolism
Muscular dystrophy
Mutation
Patients
Pediatrics
Proteins
Proteomes
Proteomics
Reproducibility of Results
Ribosomal proteins
Studies
Young Adult
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Summary:Diamond Blackfan Anemia (DBA) is a congenital anemia usually caused by diverse mutations in ribosomal proteins. Although the genetics of DBA are well characterized, the mechanisms that lead to macrocytic anemia remain unclear. We systematically analyzed the proteomes of red blood cell membranes from multiple DBA patients to determine whether abnormalities in protein translation or erythropoiesis contribute to the observed macrocytosis or alterations in the mature red blood cell membrane. In depth proteome analysis of red cell membranes enabled highly reproducible identification and quantitative comparisons of 1100 or more proteins. These comparisons revealed clear differences between red cell membrane proteomes in DBA patients and healthy controls that were consistent across DBA patients with different ribosomal gene mutations. Proteins exhibiting changes in abundance included those known to be increased in DBA such as fetal hemoglobin and a number of proteins not normally found in mature red cell membranes, including proteins involved in the major histocompatibility complex class I pathway. Most striking was the presence of dysferlin in the red blood cell membranes of DBA patients but absent in healthy controls. Immunoblot validation using red cell membranes isolated from additional DBA patients and healthy controls confirmed a distinct membrane protein signature specific to patients with DBA.
ISSN:1932-6203
1932-6203
DOI:10.1371/journal.pone.0085504