Integrin

An integrin is a transmembrane adhesion receptor linking extracellular ligands to intracellular signalling and cytoskeleton interactions. Integrin-dependent contacts transmit force in many forms of cell migration; their necessity depends on the physical environment.

LFA-1, lymphocyte function-associated antigen 1, is an integrin adhesion receptor assembled from the CD11a alpha subunit and the CD18 beta subunit. It is a heterodimer, not the name of either chain alone. Binding to intercellular adhesion molecules such as ICAM-1 helps immune cells make regulated contacts with other cells. ^[ref]

The importance of regulation became clear in an experiment linking recognition to adhesion. M. L. Dustin and T. A. Springer cross-linked the T-cell receptor and observed a rapid, transient increase in LFA-1-dependent adhesiveness toward ICAM ligands. A recognition event could therefore alter how strongly the cell attached, rather than adhesion being a permanently fixed property of its surface.^[ref]

An illuminating distinction is receptor abundance versus effective adhesion. Two cells can display similar numbers of LFA-1 molecules yet differ in the strength of contact because receptor state, organization and binding geometry differ. The reported increase in cellular avidity is a combined functional measurement; it should not automatically be read as an identical fold-change in the affinity of every isolated receptor molecule.

LFA-1 and Mac-1 share the CD18 component but use different alpha subunits. Shared machinery can support related adhesion functions without making their ligand recognition or cellular roles interchangeable.

Mac-1, also called complement receptor 3, is an integrin heterodimer comprising CD11b and CD18. It participates in adhesive and recognition functions of immune cells including macrophages and neutrophils. Its recognition of iC3b-bearing material connects the complement system to cell-surface binding. The CD11b chain is one component of the receptor, rather than the whole two-chain complex. ^[ref]

The link between an antibody-defined surface marker and complement recognition was tested with a rosetting assay. Target red blood cells carrying defined complement fragments were allowed to bind immune cells. Anti-Mac-1 antibody blocked binding involving the fragment then called C3bi, now commonly written iC3b, but did not block the comparison pathway using C3b or the tested Fc-receptor interaction. Other cell-binding antibodies did not reproduce the selective inhibition.^[ref]

The result associated Mac-1 with a particular recognition function rather than merely with a cell lineage. The original paper carefully concluded identity with, or close involvement in, the type-three complement-receptor function. Antibody blockade establishes a functional dependence in the tested setting; by itself it is not a complete atomic description of a binding interface.

Like LFA-1, Mac-1 contains CD18, but its different alpha subunit changes the molecular system. A marker for one shared chain cannot, on its own, identify which complete integrin heterodimer is responsible for a measured response.

Integrin signaling couples binding and mechanical loading of an integrin to changes inside a cell. An integrin spans the cell membrane: extracellular binding to the extracellular matrix can promote intracellular assembly of adhesion complexes connected to actin. Conversely, intracellular regulation can change integrin affinity and clustering. Signalling therefore runs in both directions across the boundary. ^[ref]

A change in matrix stiffness can change how an attached cell bears load and activates downstream signals. This makes adhesion a source of information as well as a tether. Measuring adhesion strength, phosphorylation of a signalling component and eventual cell proliferation addresses different stages; none alone specifies the whole response.