Specification of Architecture and Function of Actin Structures by Actin Nucleation Factors

Abstract

The actin cytoskeleton is essential for diverse processes in mammalian cells; these processes range from establishing cell polarity to powering cell migration to driving cytokinesis to positioning intracellular organelles. How these many functions are carried out in a spatiotemporally regulated manner in a single cytoplasm has been the subject of much study in the cytoskeleton field. Recent work has identified a host of actin nucleation factors that can build architecturally diverse actin structures. The biochemical properties of these factors, coupled with their cellular location, likely define the functional properties of actin structures. In this article, we describe how recent advances in cell biology and biochemistry have begun to elucidate the role of individual actin nucleation factors in generating distinct cellular structures. We also consider how the localization and orientation of actin nucleation factors, in addition to their kinetic properties, are critical to their ability to build a functional actin cytoskeleton.

Keywords: Arp2/3; contractile ring; formin; lamellipodium; stress fiber.

Figure 1

Different actin nucleators specify architecturally and functionally distinct actin structures. (Center) Diagram showing actin organization in a motile cell. Actin is shown in green, the Arp2/3 complex at the branch point of two filaments is shown in purple, and the FH2 homodimers of formins are shown in orange. Insets highlight organelles with associated actin structures, including vesicles, focal adhesions, mitochondria, and the nucleus, and show these structures in greater detail. Note the different geometries of actin associated with different organelles. For clarity, only the best-characterized actin nucleator is shown for each actin structure, and only some of the described actin structures are shown. Some actin structures are not depicted; these include cell–cell junctions, the contractile ring, ventral stress fibers, and blebs. Abbreviations: Arp2/3, actin-related proteins 2 and 3; DAAM1, disheveled-associated activator of morphogenesis 1; FHOD1, FH1/FH2 domain-containing protein 1; FMNL3, formin-like protein 3; INF2, inverted formin-2; mDia2, mouse diaphanous-related formin 2; TAN lines, transmembrane actin-associated nuclear lines; VASP, vasodilator-stimulated phosphoprotein.

Figure 2

Orientation of formin actin nucleators may define the geometry of linear actin structures. Formin molecules are shown in orange, and actin filaments are shown in green; the fast-growing barbed end of each filament is marked by an arrowhead. (a) Formins oriented in the same direction generate a uniform polarity bundle, for example, at the focal adhesion. A cross-linking protein specific for filaments oriented in the same direction is also shown. (b). Formins oriented back to back in linear arrays generate bundles with mixed polarity. A cross-linking protein specific for filaments oriented in the antiparallel direction is also shown, as are myosin II minifilaments. (c) Formins oriented back to back in discrete location, called pom-poms, generate isotropic networks. A cross-linking protein specific for filaments oriented in the antiparallel direction is also shown, as are myosin II minifilaments.