Description

Characterization of molecular pathways controlling cell motility is important for understanding the mechanisms involved in cell migration in normal and pathological conditions. Leukocytes circulate in search of pathogens or tissue injury, and use a connected chemokine-integrin system to traffic in and out of tissues. The integrin α4β1 mediates leukocyte migration to sites of inflammation, and its activity is regulated by chemokines, which contribute to the formation of high-affinity α4β1. Molecules which interact with the cytoplasmic domain of integrin β1 subunits such as talin, can transmit activating information from chemokine receptors to positively regulate T cell adhesion dependent on α4β1. Importantly, recent data suggest that distinct molecules compete with talin to negatively regulate β1-mediated adhesion, including ICAP-1, a protein that also interacts with the cytoplasmic domain of β1 subunits. The role of ICAP-1 on α4β1-dependent leukocyte trafficking, and the potential involvement of ICAP-1 on immune cell differentiation is being investigated using ICAP-1 knock-out mice. 

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