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Role of Lu/BCAM glycoproteins in red cell diseases.
Transfus Clin Biol. 2010 Sep; 17(3):143-7.TC

Abstract

Lu/BCAM glycoproteins (gps) are the unique erythroid receptors of laminin alpha5 chain, a major component of the extracellular matrix. They interact with the membrane skeleton by binding directly to spectrin via the Lu/BCAM RK573-574 motif. Lu/BCAM gps are involved in abnormal sickle red blood cell (RBC) adhesion to components of the vascular wall. This adhesion is activated by the phosphorylation of the Lu/BCAM long isoform Lu in a protein kinase A-dependent manner. A similar high adhesion to laminin was also observed with RBCs from Hereditary Spherocytosis (HS) patients suffering from haemolytic anaemia subsequent to spectrin deficiencies. We investigated the molecular mechanisms responsible for the Lu/BCAM-mediated abnormal RBC adhesion to laminin in sickle cell disease (SCD) and HS. We showed that SCD patients treated with hydroxycarbamide (HC) had a diminished RBC adhesion to laminin that was associated with reduced levels of the PKA upstream effector cAMP and a severe decrease in Lu isoform phosphorylation. On the other hand, we showed that increased Lu/BCAM-mediated HS RBC adhesion to laminin was independent of Lu/BCAM phosphorylation. A cellular model expressing the RK573-574AA Lu/BCAM mutant, which is unable to bind to spectrin, showed increased Lu/BCAM detergent extractability and enhanced cell adhesion to laminin. Similar results were obtained with HS RBCs, strongly suggesting that their increased adhesion could result from alteration of the Lu/BCAM-spectrin interaction following the severe spectrin deficiency.

Authors+Show Affiliations

UMRS 665, INTS, Inserm, 6, rue Alexandre-Cabanel, 75015 Paris, France. wassim.el-nemer@inserm.frNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

20655789

Citation

El Nemer, W, et al. "Role of Lu/BCAM Glycoproteins in Red Cell Diseases." Transfusion Clinique Et Biologique : Journal De La Societe Francaise De Transfusion Sanguine, vol. 17, no. 3, 2010, pp. 143-7.
El Nemer W, Colin Y, Le Van Kim C. Role of Lu/BCAM glycoproteins in red cell diseases. Transfus Clin Biol. 2010;17(3):143-7.
El Nemer, W., Colin, Y., & Le Van Kim, C. (2010). Role of Lu/BCAM glycoproteins in red cell diseases. Transfusion Clinique Et Biologique : Journal De La Societe Francaise De Transfusion Sanguine, 17(3), 143-7. https://doi.org/10.1016/j.tracli.2010.06.002
El Nemer W, Colin Y, Le Van Kim C. Role of Lu/BCAM Glycoproteins in Red Cell Diseases. Transfus Clin Biol. 2010;17(3):143-7. PubMed PMID: 20655789.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Role of Lu/BCAM glycoproteins in red cell diseases. AU - El Nemer,W, AU - Colin,Y, AU - Le Van Kim,C, Y1 - 2010/07/23/ PY - 2010/06/07/received PY - 2010/06/08/accepted PY - 2010/7/27/entrez PY - 2010/7/27/pubmed PY - 2011/1/15/medline SP - 143 EP - 7 JF - Transfusion clinique et biologique : journal de la Societe francaise de transfusion sanguine JO - Transfus Clin Biol VL - 17 IS - 3 N2 - Lu/BCAM glycoproteins (gps) are the unique erythroid receptors of laminin alpha5 chain, a major component of the extracellular matrix. They interact with the membrane skeleton by binding directly to spectrin via the Lu/BCAM RK573-574 motif. Lu/BCAM gps are involved in abnormal sickle red blood cell (RBC) adhesion to components of the vascular wall. This adhesion is activated by the phosphorylation of the Lu/BCAM long isoform Lu in a protein kinase A-dependent manner. A similar high adhesion to laminin was also observed with RBCs from Hereditary Spherocytosis (HS) patients suffering from haemolytic anaemia subsequent to spectrin deficiencies. We investigated the molecular mechanisms responsible for the Lu/BCAM-mediated abnormal RBC adhesion to laminin in sickle cell disease (SCD) and HS. We showed that SCD patients treated with hydroxycarbamide (HC) had a diminished RBC adhesion to laminin that was associated with reduced levels of the PKA upstream effector cAMP and a severe decrease in Lu isoform phosphorylation. On the other hand, we showed that increased Lu/BCAM-mediated HS RBC adhesion to laminin was independent of Lu/BCAM phosphorylation. A cellular model expressing the RK573-574AA Lu/BCAM mutant, which is unable to bind to spectrin, showed increased Lu/BCAM detergent extractability and enhanced cell adhesion to laminin. Similar results were obtained with HS RBCs, strongly suggesting that their increased adhesion could result from alteration of the Lu/BCAM-spectrin interaction following the severe spectrin deficiency. SN - 1953-8022 UR - https://www.unboundmedicine.com/medline/citation/20655789/Role_of_Lu/BCAM_glycoproteins_in_red_cell_diseases_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S1246-7820(10)00037-6 DB - PRIME DP - Unbound Medicine ER -