Drosophila type XV/XVIII collagen, Mp, is involved in Wingless distribution

Multiplexin (Mp) is the Drosophila orthologue of vertebrate collagens XV and XVIII. Like them, Mp is widely distributed in the basement membranes of the developing embryos, including those of neuroblasts in the central and peripheral nervous systems, visceral muscles of the gut, and contractile cardioblasts. Here we report the identification of mutant larvae bearing piggyBac transposon insertions that exhibit decrease Mp production associated with abdominal cuticular and wing margin defects, malformation of sensory organs and impaired sensitivity to physical stimuli. Additional findings include the abnormal ultrastructure of fatbody associated with abnormal collagen IV deposition, and reduced Wingless deposition. Collectively, these findings are consistent with the notion that Mp is required for the proper formation and/or maintenance of basement membrane, and that Mp may be involved in establishing the Wingless signaling gradients in the Drosophila embryo

A Cryptic Frizzled Module in Cell Surface Collagen 18 Inhibits Wnt/β−Catenin Signaling

Collagens contain cryptic polypeptide modules that regulate major cell functions, such as cell proliferation or death. Collagen XVIII (C18) exists as three amino terminal end variants with specific amino terminal polypeptide modules. We investigated the function of the variant 3 of C18 (V3C18) containing a frizzled module (FZC18), which carries structural identity with the extracellular cysteine-rich domain of the frizzled receptors. We show that V3C18 is a cell surface heparan sulfate proteoglycan, its topology being mediated by the FZC18 module. V3C18 mRNA was expressed at low levels in 21 normal adult human tissues. Its expression was up-regulated in fibrogenesis and in small well-differentiated liver tumors, but decreased in advanced human liver cancers. Low FZC18 immunostaining in liver cancer nodules correlated with markers of high Wnt/β−catenin activity. V3C18 (Mr = 170 kD) was proteolytically processed into a cell surface FZC18-containing 50 kD glycoprotein precursor that bound Wnt3a in vitro through FZC18 and suppressed Wnt3a-induced stabilization of β−catenin. Ectopic expression of either FZC18 (35 kD) or its 50 kD precursor inhibited Wnt/β−catenin signaling in colorectal and liver cancer cell lines, thus downregulating major cell cycle checkpoint gatekeepers cyclin D1 and c-myc and reducing tumor cell growth. By contrast, full-length V3C18 was unable to inhibit Wnt signaling. In summary, we identified a cell-surface signaling pathway whereby FZC18 inhibits Wnt/β−catenin signaling. The signal, encrypted within cell-surface C18, is released by enzymatic processing as an active frizzled cysteine-rich domain (CRD) that reduces cancer cell growth. Thus, extracellular matrix controls Wnt signaling through a collagen-embedded CRD behaving as a cell-surface sensor of proteolysis, conveying feedback cues to control cancer cell fate

Internal friction study on the mobility of screw dislocations in undoped InSb

Dislocation mobility is studied by low frequency internal friction in undoped InSb between 0.1 and 0.98 Tm. Samples characterized by a mainly screw dislocations substructure generated by low temperature (403 K) deformation, reveal two high amplitude peaks located at 570 and 725 K. The 570 K-peak symmetrically shaped is explained as an intrinsic relaxation peak of screw dislocations moving by double kink nucleation followed by their lateral propagation. The peak analysis leads to an activation energy 1.27 ± 0.11 eV, close to the apparent activation energy of the InSb plastic deformation

Internal friction study on the mobility of screw dislocations in undoped InSb

Dislocation mobility is studied by low frequency internal friction in undoped InSb between 0.1 and 0.98 Tm. Samples characterized by a mainly screw dislocations substructure generated by low temperature (403 K) deformation, reveal two high amplitude peaks located at 570 and 725 K. The 570 K-peak symmetrically shaped is explained as an intrinsic relaxation peak of screw dislocations moving by double kink nucleation followed by their lateral propagation. The peak analysis leads to an activation energy 1.27 ± 0.11 eV, close to the apparent activation energy of the InSb plastic deformation.La mobilité des dislocations a été étudiée dans InSb non dopé par frottement intérieur basse fréquence (1 Hz) entre 0,1 et 0,98 Tm. Avec une sous-structure composée essentiellement de dislocations vis engendrée par déformation plastique à 403 K, on a mis en évidence deux pics d'amplitude importante situés à 570 K et 725 K. Le pic à 570 K, d'allure symétrique, est interprété comme un pic de relaxation intrinsèque de dislocations vis par nucléation de doubles décrochements, suivie de la propagation latérale de chaque décrochement. L'analyse de ce pic conduit à une énergie d'activation de 1,27 ± 0,11 eV voisine de celle de la déformation plastique

INTERNAL FRICTION INVESTIGATION ON THE MOBILITY OF DISLOCATIONS IN III-V COMPOUNDS

La mobilité des différents types de dislocations contrôlant la déformation des composés III-V a été étudiée par des expériences de frottement intérieur entre 0,1 et 0,98 Tm sur des monocristaux d'InSb non dopés. Les résultats originaux ont été obtenus à partir de deux sous-structures de dislocations distinctes résultant de la déformation plastique en glissement simple à deux températures différentes : à 403 K où l'on obsèrve une population à caractère vis prédominant ; à 495 K où l'on observe à la fois des dislocations vis, 60° et des dipôles coins. On a ainsi mis en évidence un pic de relaxation dû aux dislocations vis dont l'énergie d'activation 1,15 eV est très proche de celle attribuée aux mouvements des dislocations vis à partir d'autres techniques et de la déformation plastique notamment.The mobility of the different types of dislocations involved in the doformation of III-V compounds has been studied with internal friction experiments from 0.1 to 0.98 Tm in undoped InSb single crystals. Original results have been achieved wiht two distinct dislocations substructures established by single glide plastic deformation at two different temperatures : 403 K, which leads to a screw dislocation predominance ; 495 K, which leads to a mixed 60°, screw, and edge dipoles substructure. We have got a relaxation peak due to screw dislocations, with an activation energy ≈ 1.15 eV, very close to that ascribed to screw dislocation movement by other techniques (plastic deformation)

High constitutive transcription of HSP86 gene in murine embryonal carcinoma cells

International audienceIn order to investigate HSP86 heat-shock gene expression in embryonal carcinoma cell lines (EC), a partial mouse HSP86 cDNA clone was isolated and characterized. As observed for the corresponding protein, HSP86 RNA is shown to be constitutively more abundant in PCC4 and undifferentiated F9 EC cells than in fibroblasts, while its amount decreases upon F9 differentiation. Although mRNA stabilization is suggested to account in part of the high constitutive expression of the heat-shock-like protein HSC73 in F9 cells, HSP86 RNA appears as stable in fibroblasts as in F9 cells. Using run-on experiments we have established that high HSP86 expression in undifferentiated F9 cells in mainly due to enhanced transcription of the gene. Possible mechanisms responsible for this high level of transcription are discussed