Chapter 2. Homo- and hetero-oligomerization of chemokines

Chemokines function in cell migration by binding and activating seven transmembrane G protein-coupled receptors (GPCRs) on leukocytes and many other diverse cell types. The extracellular binding event stabilizes specific conformations of the receptor that trigger cascades of intracellular signaling pathways involved in cell movement and activation (Baggiolini, 1998; Baggiolini et al., 1997; Charo and Ransohoff, 2006; Hartley et al., 2003; Kunkel and Butcher, 2002; Loetscher and Clark-Lewis, 2001). Although the current consensus is that monomeric forms of chemokines are necessary for receptor binding to induce cell migration, oligomeric states of chemokines may be associated with other complex functional roles such as regulation, haptotactic gradient formation, protection from proteolysis, and signaling related to processes distinct from migration. Accordingly, diverse biophysical methods have been used to identify and characterize the details of these quaternary interactions. This chapter aims to summarize these methods and to provide guidelines for their application in future studies.