Adhesive activity of Lu glycoproteins is regulated by interaction with spectrin.
The Lutheran (Lu) and Lu(v13) blood group glycoproteins function as receptors for extracellular matrix laminins. Lu and Lu(v13) are linked to the erythrocyte cytoskeleton through a direct interaction with spectrin. However, neither the molecular basis of the interaction nor its functional consequences have previously been delineated. In the present study, we defined the binding motifs of Lu and Lu(v13) on spectrin and identified a functional role for this interaction. We found that the cytoplasmic domains of both Lu and Lu(v13) bound to repeat 4 of the alpha spectrin chain. The interaction of full-length spectrin dimer to Lu and Lu(v13) was inhibited by repeat 4 of alpha-spectrin. Further, resealing of this repeat peptide into erythrocytes led to weakened Lu-cytoskeleton interaction as demonstrated by increased detergent extractability of Lu. Importantly, disruption of the Lu-spectrin linkage was accompanied by enhanced cell adhesion to laminin. We conclude that the interaction of the Lu cytoplasmic tail with the cytoskeleton regulates its adhesive receptor function.
An
Xiuli
X
Red Cell Physiology Laboratory, New York Blood Center, NY, USA.
Gauthier
Emilie
E
Zhang
Xihui
X
Guo
Xinhua
X
Anstee
David J
DJ
Mohandas
Narla
N
Chasis
Joel Anne
JA
D000268:Adhesiveness; D001665:Binding Sites; D015815:Cell Adhesion Molecules / Q000378:metabolism*; D003599:Cytoskeleton; D004912:Erythrocytes / Q000648:ultrastructure*; D006023:Glycoproteins / Q000378:metabolism*; D006801:Humans; D007797:Laminin / Q000378:metabolism; D008188:Lutheran Blood-Group System / Q000737:chemistry* / Q000378:metabolism; D011485:Protein Binding; D013049:Spectrin / Q000378:metabolism*
C090228:BCAM protein, human; D015815:Cell Adhesion Molecules; D006023:Glycoproteins; D007797:Laminin; D008188:Lutheran Blood-Group System; D013049:Spectrin