The WAVE regulatory complex is inhibited

Howard Hughes Medical Institute and Department of Biochemistry, University of Texas Southwestern Medical Center, Dallas, USA.
Nature Structural & Molecular Biology (Impact Factor: 11.63). 05/2009; 16(5):561-3. DOI: 10.1038/nsmb.1587
Source: PubMed

ABSTRACT The WAVE regulatory complex (WRC) transmits information from the Rac GTPase to the actin nucleator Arp2/3 complex. We have reconstituted recombinant human and Drosophila WRC in several forms and shown that they are inactive toward Arp2/3 complex but can be activated by Rac in a nucleotide-dependent fashion. Our observations identify core components needed for WAVE inhibition, reconcile contradictory existing mechanisms and reveal common regulatory principles for the WAVE/WASP family of proteins.

  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: During plant cell morphogenesis signal transduction and cytoskeletal dynamics interact to locally organize the cytoplasm and define the geometry of cell expansion. The WAVE (WASP-family verprolin-homologous)/SCAR (Suppressor of Cyclic AMP Receptor) regulatory complex (W/SRC) is an evolutionarily conserved heteromeric protein complex. Within the plant kingdom W/SRC is a broadly used effector that converts ROP/RAC small GTPase signals into actin-related protein (ARP) 2/3 and actin-dependent growth responses. Although the components and biochemistry of the W/SRC pathway are well understood, a basic understanding of how cells partition W/SRC into active and inactive pools is lacking. In this paper we report that the endoplasmic reticulum (ER) is an important organelle for W/SRC regulation. We determined that a large intracellular pool of the core W/SRC subunit NAP1, like the known positive regulator of W/SRC, the DOCK family guanine nucleotide exchange factor SPIKE1 (SPK1), localizes to the surface of the ER. The ER-associated NAP1 is inactive because it displays little colocalization with the actin network, and the ER localization requires neither activating signals from SPK1 nor a physical association with its W/SRC binding partner, SRA1. Our results indicate that in leaf pavement cells and trichomes, the ER is a reservoir for W/SRC signaling and may have a key role in the early steps of W/SRC assembly and/or activation.
    Plant physiology 04/2013; DOI:10.1104/pp.113.217422 · 7.39 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: The microtubule (MT) and actin cytoskeletons drive many essential cellular processes, yet fairly little is known about how their functions are coordinated. One factor that mediates important cross talk between these two systems is WHAMM, a Golgi-associated protein that utilizes MT binding and actin nucleation activities to promote membrane tubulation during intracellular transport. Using cryoelectron microscopy and other biophysical and biochemical approaches, we unveil the underlying mechanisms for how these activities are coordinated. We find that WHAMM bound to the outer surface of MT protofilaments via a novel interaction between its central coiled-coil region and tubulin heterodimers. Upon the assembly of WHAMM onto MTs, its N-terminal membrane-binding domain was exposed at the MT periphery, where it can recruit vesicles and remodel them into tubular structures. In contrast, MT binding masked the C-terminal portion of WHAMM and prevented it from promoting actin nucleation. These results give rise to a model whereby distinct MT-bound and actin-nucleating populations of WHAMM collaborate during membrane tubulation.
    The Journal of Cell Biology 10/2012; 199(1):111-24. DOI:10.1083/jcb.201204010 · 9.69 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Remodeling of the membrane and cytoskeleton is involved in a wide range of normal and pathologic cellular function. These are complex, highly-coordinated biochemical and biophysical processes involving dozens of proteins. Serving as a scaffold for a variety of proteins and possessing a domain that interacts with plasma membranes, the BAR family of proteins contribute to a range of cellular functions characterized by membrane and cytoskeletal remodeling. There are several subgroups of BAR proteins: BAR, N-BAR, I-BAR, and F-BAR. They differ in their ability to induce angles of membrane curvature and in their recruitment of effector proteins. Evidence is accumulating that BAR proteins contribute to cancer cell invasion, T cell trafficking, phagocytosis, and platelet production. In this review, we discuss the physiological function of BAR proteins and discuss how they contribute to blood and cancer disorders.
    01/2012; 3(2):198-208.


Available from