Members of the Wiskott-Aldrich Syndrome Protein (WASP) family control cytoskeletal dynamics by promoting actin filament nucleation by the Arp2/3 complex. The WASP relative, WAVE, regulates lamellipodia formation within a 400 kDa, hetero-pentameric WAVE Regulatory Complex (WRC). The WRC is inactive toward the Arp2/3 complex, but can be stimulated by the Rac GTPase, kinases and phosphatidylinositols. We report the 2.3 Å crystal structure of the WRC and complementary mechanistic analyses. The structure shows that the activity-bearing VCA motif of WAVE is sequestered by a combination of intramolecular and intermolecular contacts within the WRC. Rac and kinases appear to destabilize a WRC element that is necessary for VCA sequestration, suggesting how these signals stimulate WRC activity toward the Arp2/3 complex. Spatial proximity of the Rac binding site and a large basic surface of the WRC suggests how the GTPase and phospholipids could cooperatively recruit the complex to membranes.

SUMMARY Members of the Wiskott-Aldrich Syndrome Protein (WASP) family control actin dynamics in eukaryotic cells through stimulating the actin nucleating activity of the Arp2/3 complex. The prevailing paradigm for WASP regulation invokes allosteric relief of autoinhibition by diverse upstream activators. Here we demonstrate an additional level of regulation that is superimposed upon allostery: dimerization increases the affinity of active WASP species for Arp2/3 complex by up to 180-fold, greatly enhancing actin assembly by this system. This finding explains a large and apparently disparate set of observations under a common mechanistic framework. These include WASP activation by the bacterial effector EspFu and a large number of SH3 domain proteins, the effects on WASP of membrane localization/clustering and assembly into large complexes, and cooperativity between different family members. Allostery and dimerization act in hierarchical fashion, enabling WASP/WAVE proteins to integrate different classes of inputs to produce a wide range of cellular actin responses.

Purpose The purpose of this paper is to investigate the impact of social media marketing activities on brand loyalty, value consciousness and brand consciousness. Design/methodology/approach A self-administered questionnaire was developed and administered to a convenience sample of 346 undergraduate students Findings The findings of this research indicated that social media marketing has a significant effect on brand loyalty; brand consciousness and value consciousness mediate the relationship between social media marketing and brand loyalty. Originality/value This study confirms the growing importance of social media marketing. It also provides insights for marketers on envisioning brand loyalty.

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 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.

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SummaryVibrio cholerae is a facultative pathogen that thrives in two nutritionally disparate environments, aquatic and human small intestine. Phosphate (Pi) is an essential nutrient that is limited in aquatic ecosystems and of unknown availability in the small intestine. Here, we show that the Pi (Pho) regulon, which is controlled by the Pi-specific transporter (Pst) and two-component system PhoBR, is required for V. cholerae survival in both environments, though for differing reasons. While induction of Pi acquisition systems including Pst is critical for survival in the aquatic environment, regulation of virulence genes by PhoB and not Pi transport per se is required for colonization of the small intestine. We show that PhoB regulates virulence genes by directly controlling expression of a key upstream transcriptional regulator, tcpPH. Thus, the Pho regulon includes virulence genes and represents a diverse gene set essential to pathogenic V. cholerae throughout its life cycle.