IRSp53: crossing the road of membrane and actin dynamics in the formation of membrane protrusions

A tight spatiotemporal coordination of the machineries controlling membrane bending and trafficking, and actin dynamics is crucial for the generation of cellular protrusions. Proteins that are simultaneously capable of regulating actin dynamics and sensing or inducing membrane curvature are predicted to have a prominent role. A prototypical example of this type of proteins is the insulin receptor tyrosine kinase substrate of 53 kDa, the founding member of a recently discovered family of proteins, including missing-in-metastasis and ABBA (actin-bundling protein with BAIAP2 homology). Structural, biochemical and cell biological experiments support the unique role of this family as transducers of signalling, linking the protruding membrane to the underlying actin cytoskeleton.