WAVE/SCAR protein was identified as a protein which has similarity to WASP and N-WASP, especially in its C terminal. Recently, WAVE/SCAR protein has been shown to cooperate with the Arp2/3 complex, a ...nucleation core for actin polymerization in vitro. However, in spite of its general function, WAVE/SCAR expression is mainly restricted to the brain, suggesting the existence of related molecule(s). We here identified two human WAVE/SCAR homologues, which cover other organs. We named the original WAVE1 and newly identified ones WAVE2 and WAVE3. WAVE2 had a very wide distribution with strong expression in peripheral blood leukocytes and mapped on chromosome Xp11.21, next to the WASP locus. WAVE3 and WAVE1 had similar distributions. WAVE3 was strongly expressed in brain and mapped on chromosome 13q12. WAVE1 was mapped on chromosome 6q21-22. Ectopically expressed WAVE2 and WAVE3 induced actin filament clusters in a similar manner with WAVE1. These actin cluster formations were suppressed by deletion of their C-terminal VPH (verproline homology)/WH2 (WASP homology 2) domain. Further, WAVE2 and WAVE3 associate with the Arp2/3 complex as does WAVE1. Our identification of WAVE homologues suggests that WAVE family proteins have general function for regulating the actin cytoskeleton in many tissues.
N-WASP is a member of the WASP family of proteins that regulate actin cytoskeleton remodeling. FAK is a cytoplasmic tyrosine kinase implicated in integrin signaling during cell migration. Here we ...identify a direct interaction between N-WASP and FAK and show that N-WASP is phosphorylated by FAK at a conserved tyrosine residue, Tyr256. We found that phosphorylation of Tyr256 affected N-WASP nuclear localization, suggesting that phosphorylation of N-WASP by FAK may regulate its activity in vivo by altering its subcellular localization. We also showed that the nuclear localization of N-WASP is dependent on its being in the open conformation either after its activation by Cdc42 or the truncation of the C-terminal VCA domain. Phosphorylation of Tyr256 of N-WASP could reduce its interaction with nuclear importin NPI-1, which might be responsible for its decreased nuclear localization. Lastly, we show that phosphorylation of Tyr256 plays an important role in promoting cell migration. Together, these results suggest a novel regulatory mechanism of N-WASP by tyrosine phosphorylation and subcellular localization and its potential role in the regulation of cell migration.
In Dirac semimetals, interband mixing has been known theoretically to give rise to a giant orbital diamagnetism when the Fermi level is close to the Dirac point. In Bi 1−x Sbx and other Dirac ...semimetals, an enhanced diamagnetism in the magnetic susceptibility χ has been observed and interpreted as a manifestation of such giant orbital diamagnetism. Experimentally proving their orbital origin, however, has remained challenging. The cubic antiperovskite Sr3PbO is a three-dimensional Dirac electron system and shows the giant diamagnetism in χ as in the other Dirac semimetals. 207Pb NMR measurements are conducted in this study to explore the microscopic origin of diamagnetism. From the analysis of the Knight shift K as a function of χ and the relaxation rate T1–1 for samples with different hole densities, the spin and the orbital components in K are successfully separated. The results establish that the enhanced diamagnetism in Sr3 PbO originates from the orbital contribution of Dirac electrons, which is fully consistent with the theory of giant orbital diamagnetism.
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