Protein modules as organizers of membrane structure

Investigations conducted over the past 18 months have shed new light on how modular protein-binding domains, in particular PDZ domains, co-ordinate th e assembly of functional plasma membrane domains. Members of the MAGUK (mem brane-associated guanylate kinase) protein family, like PSD-95, use multipl e domains to cluster ion channels, receptors, adhesion molecules and cytoso lic signaling proteins at synapses, cellular junctions, and polarized membr ane domains. Other PDZ proteins, like the Drosophila protein INAD and the e pithelial Na+/H+ regulatory factor (NHERF), organize cellular signaling by localizing transmembrane and cytosolic components to specific membrane doma ins and assembling these components into functional complexes. The organiza tion of these proteins into discreet structures has functional consequences for downstream signaling.