TY - JOUR
T1 - Bimolecular complex between rolling and firm adhesion receptors required for cell arrest
T2 - CD44 association with VLA-4 in T cell extravasation
AU - Nandi, Animesh
AU - Estess, Pila
AU - Siegelman, Mark
N1 - Funding Information:
This work was supported grants from the NIH (R01 HL56746, to M.S.) and the Burroughs Wellcome Fund (to M.S.). We gratefully acknowledge Jayne Lesley for the CD44-transfected cell lines; and Sohita Dhillon and Ray Velasco for invaluable assistance.
PY - 2004/4
Y1 - 2004/4
N2 - CD44 on activated T cells can initiate contact and mediate rolling on hyaluronan on endothelial cells. We have shown that the integrin VLA-4 is used preferentially over LFA-1 in conjunction with this rolling interaction for firm adhesion. Here, we show by coimmunoprecipitation and transfection studies that CD44 associates with VLA-4 but not LFA-1 on the plasma membrane of immune cells. Absence of the cytoplasmic portion of CD44 abrogates this coassociation and attendant firm adhesion. Moreover, in an in vivo model of lymphocyte homing, cells expressing only the truncated form of CD44 together with VLA-4 fail to traffic to an inflamed site, thereby defining a discrete biological role for the cytoplasmic domain. These studies demonstrate a molecular mechanism whereby coanchoring within a single bimolecular complex between a primary and secondary adhesion molecule regulates a cell's ability to firmly adhere, providing a fundamental alteration to the paradigm of leukocyte extravasation.
AB - CD44 on activated T cells can initiate contact and mediate rolling on hyaluronan on endothelial cells. We have shown that the integrin VLA-4 is used preferentially over LFA-1 in conjunction with this rolling interaction for firm adhesion. Here, we show by coimmunoprecipitation and transfection studies that CD44 associates with VLA-4 but not LFA-1 on the plasma membrane of immune cells. Absence of the cytoplasmic portion of CD44 abrogates this coassociation and attendant firm adhesion. Moreover, in an in vivo model of lymphocyte homing, cells expressing only the truncated form of CD44 together with VLA-4 fail to traffic to an inflamed site, thereby defining a discrete biological role for the cytoplasmic domain. These studies demonstrate a molecular mechanism whereby coanchoring within a single bimolecular complex between a primary and secondary adhesion molecule regulates a cell's ability to firmly adhere, providing a fundamental alteration to the paradigm of leukocyte extravasation.
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U2 - 10.1016/S1074-7613(04)00077-9
DO - 10.1016/S1074-7613(04)00077-9
M3 - Article
C2 - 15084274
AN - SCOPUS:1842633889
SN - 1074-7613
VL - 20
SP - 455
EP - 465
JO - Immunity
JF - Immunity
IS - 4
ER -