The Lutheran glycoprotein: a multifunctional adhesion receptor

The Lutheran blood group system, which comprises one of the largest families of human red blood cell (RBC) antigens, resides on two immunoglobulin superfamily (IgSF) proteins: Lutheran and basal cell adhesion molecule (B-CAM). These two glycoproteins arise via alternative splicing of mRNA from a single gene and differ in structure only in the lengths of their cytoplasmic tails. Both are expressed on RBCs as well as a variety of other cell types, and they are overexpressed on sickle RBCs (SS RBC). B-CAM/Lu is the critical receptor for SS RBC adhesion to the extracellular matrix protein laminin, an interaction thought to contribute to the pathogenesis of sickle cell-related vasoocclusive events. Recent work has also shown that B-CAM/Lu on RBCs can undergo activation as a result of adrenergic signaling pathways. The high affinity of B-CAM/Lu for laminin is also thought to contribute to various developmental processes, including organogenesis, vascular development, erythropoiesis, and smooth muscle development and organization. Interestingly, the B-CAM spliceoform seems to be overexpressed by a variety of different malignant tumors and may be involved, along with other adhesion receptor proteins, in malignant transformation and tumor metastasis. Studies of B-CAM/Lu have thus expanded from defining antigen-specific polymorphisms to investigations of processes involved in sickle cell disease, human development, and cancer biology.