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Neural Wiskott-Aldrich syndrome protein (N-WASP) and WAVE are members of a family of proteins that use the Arp2/3 complex to stimulate actin assembly in actin-based motile processes. By entering into distinct macromolecular complexes, they act as convergent nodes of different signalling pathways. The role of WAVE in generating lamellipodial protrusion during cell migration is well established. Conversely, the precise cellular functions of N-WASP have remained elusive. Here, we report that Abi1, an essential component of the WAVE protein complex, also has a critical role in regulating N-WASP-dependent function. Consistently, Abi1 binds to N-WASP with nanomolar affinity and, cooperating with Cdc42, potently induces N-WASP activity in vitro. Molecular genetic approaches demonstrate that Abi1 and WAVE, but not N-WASP, are essential for Rac-dependent membrane protrusion and macropinocytosis. Conversely, Abi1 and N-WASP, but not WAVE, regulate actin-based vesicular transport, epidermal growth factor receptor (EGFR) endocytosis, and EGFR and transferrin receptor (TfR) cell-surface distribution. Thus, Abi1 is a dual regulator of WAVE and N-WASP activities in specific processes that are dependent on actin dynamics.

The Rho-GTPase Rac1 stimulates actin remodelling at the cell periphery by relaying signals to Scar/WAVE proteins leading to activation of Arp2/3-mediated actin polymerization. Scar/WAVE proteins do not interact with Rac1 directly, but instead assemble into multiprotein complexes, which was shown to regulate their activity in vitro. However, little information is available on how these complexes function in vivo. Here we show that the specifically Rac1-associated protein-1 (Sra-1) and Nck-associated protein 1 (Nap1) interact with WAVE2 and Abi-1 (e3B1) in resting cells or upon Rac activation. Consistently, Sra-1, Nap1, WAVE2 and Abi-1 translocated to the tips of membrane protrusions after microinjection of constitutively active Rac. Moreover, removal of Sra-1 or Nap1 by RNA interference abrogated the formation of Rac-dependent lamellipodia induced by growth factor stimulation or aluminium fluoride treatment. Finally, microinjection of an activated Rac failed to restore lamellipodia protrusion in cells lacking either protein. Thus, Sra-1 and Nap1 are constitutive and essential components of a WAVE2- and Abi-1-containing complex linking Rac to site-directed actin assembly.

Signal-dependent regulation of actin dynamics is essential for a variety of cellular processes, including formation of the membrane protrusions required for cell locomotion. Wiskott-Aldrich syndrome protein (WASP), neural (N)-WASP and WASP family verprolin-homologous (WAVE, also named Scar) proteins are thought to play a role in these processes by relaying activation signals from small GTPases, such as Cdc42 and Rac, to the actin-nucleating complex Arp2/3. Although much biochemical and structural biological work has defined the paradigms through which WASP and N-WASP regulation is achieved, only recently have the mechanisms that control WAVE proteins begun to be clarified. WAVE proteins assemble into macromolecular complexes, which are essential for the regulation of WAVE nucleation-promoting activity, dynamic localization and stability. In this article, we discuss recent studies that highlight novel modalities through which WAVE proteins are regulated and, in turn, mediate the site-directed actin polymerization required for membrane protrusion, thus enabling cell motility.

Abl interactor 1 (Abi1) plays a critical function in actin cytoskeleton dynamics through participation in the WAVE2 complex. To gain a better understanding of the specific role of Abi1, we generated a conditional Abi1-KO mouse model and MEFs lacking Abi1 expression. Abi1-KO cells displayed defective regulation of the actin cytoskeleton, and this dysregulation was ascribed to altered activity of the WAVE2 complex. Changes in motility of Abi1-KO cells were manifested by a decreased migration rate and distance but increased directional persistence. Although these phenotypes did not correlate with peripheral ruffling, which was unaffected, Abi1-KO cells exhibited decreased dorsal ruffling. Western blotting analysis of Abi1-KO cell lysates indicated reduced levels of the WAVE complex components WAVE1 and WAVE2, Nap1, and Sra-1/PIR121. Although relative Abi2 levels were more than doubled in Abi1-KO cells, the absolute Abi2 expression in these cells amounted only to a fifth of Abi1 levels in the control cell line. This finding suggests that the presence of Abi1 is critical for the integrity and stability of WAVE complex and that Abi2 levels are not sufficiently increased to compensate fully for the loss of Abi1 in KO cells and to restore the integrity and function of the WAVE complex. The essential function of Abi1 in WAVE complexes and their regulation might explain the observed embryonic lethality of Abi1-deficient embryos, which survived until approximately embryonic day 11.5 and displayed malformations in the developing heart and brain. Cells lacking Abi1 and the conditional Abi1-KO mouse will serve as critical models for defining Abi1 function., Journal Article, Research Support, N.I.H. Extramural, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, Non-P.H.S., info:eu-repo/semantics/published

NR 20150402

Implantation of B has been performed into an epitaxially grown layer of 6H SiC, at two different B concentrations, 2 x 10(16) cm(-3) and 2 x 10(18) cm(-3). Subsequently, an epitaxial layer was regrown on the B implanted layer. The samples were investigated by transmission electron microscopy (TEM) and secondary ion mass spectrometry (SIMS). In the highly B-doped layers plate-like defects were found, associated with large strain fields, and an increased B concentration. These defects were stable at the originally implanted region during regrowth and at anneal temperatures up to 1700 degrees C. In the samples implanted with the lower B concentration, no crystal defects could be detected by TEM. No threading dislocations or other defects were observed in the regrown epitaxial layer, which shows the possibility to grow a layer with high crystalline quality on B implanted 6H SiC. By SIMS, it was found that B piles up at the interface to the regrown layer, which could be explained by enhanced diffusion from an increased concentration of point defects created by implantation damage in the region. B is also spread out into the original crystal and in the regrown layer at a concentration of below 2 x 10(16) cm(-3), with a diffusion constant estimated to 1.3 x 10(-12) cm(2)s(-1). This diffusion is most probably not driven by implantation damage, but by intrinsic defects in the grown crystal. Our investigation shows that the combination of implantation and subsequent regrowth techniques could be used in SiC for building advanced device structures, with the crystal quality in the regrown layer not being deteriorated by crystal defects in the implanted region. A device process using B implantation and subsequent regrowth could on the other hand be limited by the diffusion of B., QC 20150624

The Junction Barrier Schottky (JBS) diode in silicon carbide is a promising candidate for a low-leakage power rectifier for high switching frequencies and elevated temperature operation. It has the advantage of a low forward voltage drop while keeping a low leakage current at high blocking voltage. JBS devices have been fabricated in 4H SiC and 6H SiC and then electrically characterised in comparison with pn and Schottky diodes on the same wafer. The JBS devices reached blocking voltages up to 1.0 kV at a leakage current density of 13 ÎŒA/cm2 and the forward conduction was limited by an on-resistance close to the theoretical value., References: Bhatnagar, M., Baliga, B.J., Kirk, H.R., Rozgonyi, G.A., (1996) IEEE Trans. Electron Devices, 43, p. 150; Crofton, J., Sriram, S., (1996) IEEE Trans. Electron Devices, 43, p. 2305; Baliga, B.J., (1984) IEEE Electron Device Letters, 5, p. 194; Baliga, B.J., (1985) Solid-State Electron., 28, p. 1089; Biersack, J.P., Haggmark, L.G., (1980) Nucl. Instr. and Meth., 174, p. 257; Pensl, G., Afanas'ev, V.V., Bassler, M., Schadt, M., Troffer, T., Heindl, J., Strunk, H.P., Choyke, W.J., (1995) Inst. Phys. Conf. Ser., 142, p. 275; Afanas'ev, V.V., Bassler, M., Pensl, G., Schulz, M.J., (1996) J. Appl. Phys., 79, p. 3108; Schaffer, W.J., Negley, G.H., Irvine, K.G., Palmour, J.W., (1994) Mat. Res. Soc. Symp. Proc., 339, p. 595; Itoh, A., Kimoto, T., Matsunami, H., (1995) Inst. Phys. Conf. Ser., 142, p. 689 NR 20140805

Junction barrier Schottky (JBS) diodes in 6H SiC have been fabricated and characterised electrically. This device, demonstrated in silicon technology, has the advantage of a low forward voltage drop comparable to that of Schottky diodes, as well as a high blocking voltage and low reverse leakage current of a pn junction. This is especially attractive for wide bandgap materials such as SiC in which pn junctions have a large forward voltage drop. The devices were capable of blocking up to 1100 V with a leakage current density of 0.15 A cm-2, limited by the leakage when the drift region was fully depleted, or breakdown of the SiC material itself. The forward conduction was limited by an on-resistance of 20 mΩ cm2, resulting in forward voltage drops of 2.6 V at 100 A cm-2. © 1998 Published by Elsevier Science Ltd. All rights reserved., References: Crofton, J., Sriram, S., (1996) IEEE Trans. Electron Devices, 43, p. 2305; Bhatnagar, M., Baliga, B.J., Kirk, H.R., Rozgonyi, G.A., (1996) IEEE Trans. Electron Devices, 43, p. 150; Kimoto, T., Urushidani, T., Kobayashi, S., Matsunami, H., (1993) IEEE Electron Device Lett., 14, p. 548; Lundberg, N., Östling, M., TÀgtström, P., Jansson, U., (1996) J. Electrochem. Soc., 143, p. 1662; Baliga, B.J., (1984) IEEE Electron Device Lett., 5, p. 194; Baliga, B.J., (1985) Solid-State Electron., 28, p. 1089; Biersack, J.P., Haggmark, L.G., (1980) Nucl. Instrum. Methods, 174, p. 257; Ziegler, J.F., Biersack, J.P., Littmark, U., (1985) The Stopping and Range of Ions in Solids, 1. , ed. J. F. Ziegler. Pergamon, New York; Pensl, G., Afanas'ev, V.V., Bassler, M., Schadt, M., Treffer, T., Heindl, J., Strunk, H.P., Choyke, W.J., (1995) Inst. Phys. Conf. Ser., 142, p. 275; Waldrop, J.R., Grant, R.W., (1993) Appl. Phys. Lett., 62, p. 2685; Itoh, A., Kimoto, T., Matsunami, H., (1995) Inst. Phys. Conf. Ser., 142, p. 689 NR 20140805

Silicon carbide is due to its wide bandgap, high saturated electron drift velocity, high electric breakdown field and high thermal conductivity a suitable material for electron devices operating at high temperatures, high powers and high frequencies.[1,2] In order for SIC to reach its full potential in device technology, doping is essential. Usually ion implantation is used for doping since diffusion is difficult in SiC. Boron is a useful material for implantation because of its low atomic weight and greater penetration depth than other accepters, yet very few studies have been conducted on B-implanted 6H-SiC. [3,4] In this investigation we have used transmission electron microscopy (TEM) to study structural defects that are found in B-implanted 6H-SiC layers., QC 20150315

Platinum-oxide-silicon carbide structures change their capacitance upon gas exposure and are used as gas sensors. The decrease of the inversion capacitance within 750 to 900 degrees C due to hydrogen exposure is studied for 4H- and 6H-SiC,:both n- and p-type. A mechanism for the capacitance decrease is suggested which explains also the large change in the conductance of the structures.

The incorporation of hydrogen during vapor phase epitaxy was investigated using secondary ion mass spectroscopy, low temperature photoluminescence, and capacitance-voltage measurements. It was found that hydrogen incorporation is strongly dependent on the concentration of the acceptor dopants aluminum and boron, regardless of changes in the doping concentration caused by varying the concentration ratio between carbon and silicon or the dopant precursor flow. An electrical passivation of the acceptor dopants was found and could be reduced by annealing at temperatures above 1000 degrees C. At the same anneal temperature hydrogen-related photoluminescence was considerably reduced and the diffusion of hydrogen was detected. (C) 1997 Elsevier Science S.A., 1st European Conference on Silicon Carbide and Related Materials (ECSCRM 96), IRAKLION, GREECE, OCT 06-09, 1996 NR 20140805

Derwent Primary Accession Number: 1997-489903 . QS 201504

Hall-effect measurements on aluminium (Al)-doped p-type 6H-SiC were made and the dependence of the Al ionization energy on doping concentration and compensation was investigated. It is shown that the Al ionization energy is almost constant for a degree of compensation K much less than 0.01 up to an Al concentration of 5 . 10(20)cm(-3). An average value for the Al ionization energy is found to be 241.6 +/- 5.2 meV. Additionally, we find that the Al ionization energy for a degree of compensation in a range of 0.01 to 0.5 varies with doping concentration and compensation. An impurity band model describing this dependence is discussed., QC 20150313