PubMed Health⌕ Search

Biomedical subjects

Pierre-Olivier Schischmanoff

Publications and source records attributed to Pierre-Olivier Schischmanoff.

5 recordsLinked to original sources
PubMed2003

Abnormal glycosylation of red cell membrane band 3 in the congenital disorder of glycosylation Ig.

A description is provided of the clinical presentation in an infant of the recently described congenital disorder of glycosylation type Ig, and the changes affecting glycosylation of red cell membrane band 3, the anion exchanger. It has been shown that the condition stems from a homozygous mutation within the human ortholog of yeast ALG12 gene, which encodes a dolichol-P-mannose:Man7GlcNAc2-PP-dolichol alpha,1-6 mannosyltransferase of the endoplasmic reticulum. The clinical phenotype included prominent central and peripheral manifestations in the CNS. Although the infant studied had no anemia, band 3 abnormally separated into two fractions upon electrophoresis. The chemical composition of the glycans of both fractions was analyzed in detail. The fraction with low electrophoretic mobility was moderately hypoglycosylated (by 27%) and its mannose content was normal. The fraction with high electrophoretic mobility was deeply carbohydrate deficient (by 64%) and had 1 mol mannose in excess but only three residues of N-acetylglucosamine. Glycophorin A was hypoglycosylated with respect to O-linked glycans. Glycosphingolipids of red cells were normal. We suggest that the incomplete biosynthesis of the N-linked glycan of band 3 was largely caused by the persistence of the 3-linked mannose residue on the 6-mannose arm of the trimannosyl moiety of the glycoprotein. It is remarkable that the changes recorded in band 3 have no clinical consequences. Band 3 alteration might serve as an additional indicator (some serum N-glycoproteins of hepatic origin are also indicative) of the congenital disorder of glycosylation type Ig.

Anion Exchange Protein 1, Erythrocyte↗
PubMed2002

Congenital dyserythropoietic anemia type I is caused by mutations in codanin-1.

Congenital dyserythropoietic anemias (CDAs) constitute a rare group of inherited red-blood-cell disorders associated with dysplastic changes in late erythroid precursors. CDA type I (CDAI [MIM 224120], gene symbol CDAN1) is characterized by erythroid pathological features such as internuclear chromatin bridges, spongy heterochromatin, and invagination of the nuclear membrane, carrying cytoplasmic organelles into the nucleus. A cluster of 45 highly inbred Israeli Bedouin with CDAI enabled the mapping of the CDAN1 disease gene to a 2-Mb interval, now refined to 1.2 Mb, containing 15 candidate genes on human chromosome 15q15 (Tamary et al. 1998). After the characterization and exclusion of 13 of these genes, we identified the CDAN1 gene through 12 different mutations in 9 families with CDAI. This 28-exon gene, which is transcribed ubiquitously into 4738 nt mRNA, was reconstructed on the basis of gene prediction and homology searches. It encodes codanin-1, a putative o-glycosylated protein of 1,226 amino acids, with no obvious transmembrane domains. Codanin-1 has a 150-residue amino-terminal domain with sequence similarity to collagens and two shorter segments that show weak similarities to the microtubule-associated proteins, MAP1B (neuraxin) and synapsin. These findings, and the cellular phenotype, suggest that codanin-1 may be involved in nuclear envelope integrity, conceivably related to microtubule attachments. The specific mechanisms by which codanin-1 underlies normal erythropoiesis remain to be elucidated.

Amino Acid Sequence↗
PubMed2002

A splicing alteration of 4.1R pre-mRNA generates 2 protein isoforms with distinct assembly to spindle poles in mitotic cells.

The C-terminal region of erythroid cytoskeletal protein 4.1R, encoded by exons 20 and 21, contains a binding site for nuclear mitotic apparatus protein (NuMA), a protein needed for the formation and stabilization of the mitotic spindle. We have previously described a splicing mutation of 4.1R that yields 2 isoforms: One, CO.1, lacks most of exon 20-encoded peptide and carries a missense C-terminal sequence. The other, CO.2, lacks exon 20-encoded C-terminal sequence, but retains the normal exon 21-encoded C-terminal sequence. Knowing that both shortened proteins are expressed in red cells and assemble to the membrane skeleton, we asked whether they would ensure 4.1R mitotic function in dividing cells. We show here that CO.2, but not CO.1, assembles to spindle poles, and colocalizes with NuMA in erythroid and lymphoid mutated cells, but none of these isoforms interact with NuMA in vitro. In microtubule-destabilizing conditions, again only CO.2 localizes to the centrosomes. These data suggest that the stability of 4.1R association with centrosomes requires an intact C-terminal end, either for a proper conformation of the protein, for a direct binding to an unknown centrosome-cytoskeletal network, or for both. We also found that 4.1G, a ubiquitous homolog of 4.1R, is present in mutated as well as control cells and that its C-terminal region binds efficiently to NuMA, suggesting that in fact mitotic spindles host a mixture of the two 4.1 family members. These findings led to the postulate that the coexpression at the spindle poles of 2 related proteins, 4.1R and 4.1G, might reflect a functional redundancy in mitotic cells.

Alternative Splicing↗