Signalling mechanisms of the leukocyte integrin αMβ2: Current and future perspectives

Integrins are a family of heterodimeric cell adhesion receptors expressed on most cells and are involved in many cellular functions including phagocytosis, a process by which professional phagocytes recognise, bind and internalise foreign materials larger than 0.5 μm in diameter. An example of a phagocytic integrin receptor is αMβ2, and this review seeks to provide fresh insights into the current knowledge of this subject. Key areas that this review will emphasise include, the classical understanding of bi-directional signalling to and from αMβ2 (aka inside-out and outside-in signalling, respectively). For inside-out signalling, we will review the involvement of the small GTPase, Rap1, FERM-containing proteins such as talin and kindlin-3, some of the kinases, and the GEF, cytohesin-1 and vasodilator-stimulated phosphoprotein (VASP). We also summarise studies into outside-in signalling, focussing on the roles of RhoA and RhoG, and activation of Rac1 through the complex comprising TIAM, 14-3-3 and β2. We will also consider non-classical signalling processes, which include integrin clustering and membrane ruffling. Through this review, we hope to highlight the importance of αMβ2 signalling mechanisms and their relevance to other integrin-mediated events.