Abstract
Very Late Antigen-4 (CD49d/CD29, alpha4 beta1) and Lymphocyte Function-associated Antigen-1 (CD11a/CD18, alphaL beta2) integrins are representatives of a large family of adhesion receptors widely expressed on immune cells. They participate in cell recruitment to sites of inflammation, as well as multiple immune cell interactions. A unique feature of integrins is that integrin-dependent cell adhesion can be rapidly and reversibly modulated in response to cell signaling, because of a series of conformational changes within the molecule, which include changes in the affinity of the ligand binding pocket, molecular extension (unbending) and others. Here, we provide a concise comparative analysis of the conformational regulation of the two integrins with specific attention to the physiological differences between these molecules. We focus on recent data obtained using a novel technology, based on small fluorescent ligand-mimicking probes for the detection of integrin conformation in real-time on live cells at natural receptor abundance.
Highlights
Integrins are a large family of adhesion receptors widely expressed on different cell types that participate in cell-matrix, or cell-cell interactions
To study the real-time regulation of integrin affinity and conformation, we developed a set of small fluorescent probes. [For VLA-4 see (Chigaev et al, 2001, 2003b, 2004) and for LFA1 see (Chigaev et al, 2011b)]
The ability of VLA-4 to bind ligand in the low affinity resting state as well as the high affinity activated state allows it to serve as an adhesion receptor for rolling as well as firm attachment
Summary
Integrins are a large family of adhesion receptors widely expressed on different cell types that participate in cell-matrix, or cell-cell interactions. Ligation of other receptors, including different G-protein coupled receptors, cytokine, and chemokine receptors, Fc-receptors and others, can lead to the propagation of an inside-out signal toward the integrin (Hogg et al, 2011) This can result in a series of conformational changes within integrin molecules leading to a rapid increase or decrease of the integrin ligand binding affinity, molecular extension (unbending), movement of integrin domains (such as hybrid domain swing-out), and changes in integrin lateral mobility. These events directly modulate cell adhesion behavior (Askari et al, 2009). Even though teleost fish and several tunicata genomes contain integrin alpha subunits that have the inserted alpha I-domain, the leukocyte-specific integrin subunit orthologs, which include alpha D, alpha M, alpha X, and www.frontiersin.org
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