Unraveling the enigma: progress towards understanding the coronin family of actin regulators

Abstract

Coronins are a conserved family of actin cytoskeleton regulators that promote cell motility and modulate other actin-dependent processes. Although these proteins have been known for 20 years, substantial progress has been made in the past 5 years towards their understanding. In this review, we examine this progress, place it into the context of what was already known, and pose several questions that remain to be addressed. In particular, we cover the emerging consensus about the role of Type I coronins in coordinating the function of Arp2/3 complex and ADF/cofilin proteins. This coordination plays an important role in leading-edge actin dynamics and overall cell motility. Finally, we discuss the roles played by the more exotic coronins of the Type II and III classes in cellular processes away from the leading edge.

Figure 1

Schematic of coronin structural domain arrangement. Type I and Type II coronins share similar structural organization, including an N-terminal extension (N), a β-propeller, a C-terminal extension (C), a unique region (U) and a coiled-coil domain (CC). In Type I and type II coronins, the coiled-coil domain is involved in coronin oligomerization. Type III coronins lack a coiled-coil domain but instead comprise two β-propellers (with N- and C-terminal extensions) and an acidic region (A).

Figure 2

Integrated model of Type I coronin function Coronin is a coordinating factor between Arp2/3-based actin assembly and cofilin-mediated disassembly. In the context of lamellipodia, at the leading edge the Arp2/3 complex promotes actin assembly by binding existing actin filaments and nucleating new actin branches. Coronin limits Arp2/3-dependent actin branches through inhibition of Arp2/3 docking or facilitating debranching, a function which is antagonized by cortactin. Coronin can replace Arp2/3 at actin branches and create more flexible branches. At the lamellipodia rear, cofilin facilitates actin disassembly. Coronin enhances the activity of cofilin either directly or by targeting the slingshot phosphatase. In addition, coronin may synergize with AIP1. Dashed lines indicate interactions that have only been seen in one species or require further validation by functional studies in vivo.