CYRI/ Fam49 Proteins Represent a New Class of Rac1 Interactors.

Fam49 proteins, now referred to as CYRI (CYFIP-related Rac Interactor), are evolutionarily conserved across many phyla. Their closest relative by amino acid sequence is CYFIP, as both proteins contain a domain of unknown function DUF1394. We recently showed that CYRI and the DUF1394 can mediate binding to Rac1 and evidence is building to suggest that CYRI plays important roles in cell migration, chemotaxis and pathogen entry into cells. Here we discuss how CYRI proteins fit into the current framework of the control of actin dynamics by positive and negative feedback loops containing Rac1, the Scar/WAVE Complex, the Arp2/3 Complex and branched actin. We also provide data regarding the interaction between Rac1 and CYRI in an unbiassed mass spectrometry screen for interactors of an active mutant of Rac1.