Targeting of SCG10 to the Area of the Golgi Complex Is Mediated by Its NH2-terminal Region

Paolo, Gilbert Di; Lütjens, Robert; Pellier, Véronique; Stimpson, Stephen A.; Beuchat, Marie-Hélène; Catsicas, Stefan; Grenningloh, Gabriele

doi:10.1074/jbc.272.8.5175

Cited by 92 publications

(95 citation statements)

References 32 publications

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“…It is, therefore, of interest that SCGlO and RB3 were both recovered in the particulate fraction and were thus most likely membrane bound, whereas stathmin is essentially cytosoluble [ l ] ; SCGlO was further shown to be present in the perinuclear region and in growth cones and is probably a vesicle-associated protein [36]. As the sequences of SCGIO and RB3RB3' do not contain any feature of a transmembrane protein, it is likely that RB3/RB3' are indeed palmitoylated in the cell as has been recently shown for SCGlO [44], and that this posttranslational modification contributes to their partial membrane association. This specific subcellular localization might participate in the functional specificity of the SCGIO and RB3/RB3' proteins, as compared to stathmin.…”

Section: Discussionmentioning

confidence: 95%

“…However, no hydrophobic sequence of sufficient length for membrane spanning was identified within this A domain, but two closely located conserved cysteins at positions 20 and 22 within the A domain of SCGlO might constitute a palmitoylation site [44] (for a review, see [45]) responsible for its partial membrane binding. These two cystein residues are also conserved within the N-terminal A domain of RB3/RB3' (Figs 2, 3), as well as in the Xenopus XB3 sequence [34], which suggests that the RB3 and RB3' proteins are, as is SCG10, at least partially membrane Identification of protein forms.…”

Section: Rb3/rb3' C a C T C C T T G T G A C T T T T G G T C A A T T Cmentioning

confidence: 99%

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The Stathmin Family

Ozon

Maucuer

Sobel

1997

European Journal of Biochemistry

111

102

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Stathmin is a ubiquitous phosphoprotein proposed to be a relay integrating various intracellular signaling pathways. Its high phylogenetic conservation and the identification of the related molecules, SCGIO in rat and XB3 in Xenopus, suggested the existence of a stathmin-related family. A systematic PCR-based approach allowed the identification of several novel mammalian sequences of which two coded for expressed members of the stathmin family; the translated RB3 sequence shares 88 % amino-acid identity with that of XB3 and is thus its rat homologue, and RB3' corresponds to an alternatively spliced product of the same gene, encoding a truncated form. Within their stathmin-like domain, the a helix, probably responsible for coiled-coil protein-protein interactions, is conserved, as well as are two consensus phosphorylation sites ; in their N-terminal extension domain, two cystein residues most likely responsible for membrane attachment through palmitoylation, are present in RB3/RB3' as in SCGIO. The novel identification and characterization of the corresponding proteins showed that all three are associated with the particulate, membrane-containing fraction. They furthermore display several spots of decreasing PI on two-dimensional immunoblots, suggesting that they are phosphorylated in uiuo. As for SCGIO, RB3 mRNA is detectable only in the nervous system by in situ hybridization, but at similar levels in the newborn and the adult brain as revealed by Northern blots, whereas SCGlO expression decreases in the adult. Furthermore, RB3 mRNA is undetectable in PC12 cells, whereas SCGlO mRNA increases after treatment with nerve growth factor, inducing neuronal differentiation. In conclusion, we demonstrate here the existence of a highly conserved stathmin-related family in mammals, of which each member seems to play specific roles, related to the control of cell proliferation and activities for stathmin and to that of neuronal differentiation for SCG10, the novel RBYRB3' proteins being rather related to the expression of differentiated neuronal functions. phosphorylation of its regulatory domain, conveying them to diverse target proteins 127, 331. In addition to its high molecular and biological conservation among vertebrates [4, 341, stathmin was identified as the generic element of a molecular family, of which two other members, SCGlO and XB3, have been identified previously. SCG10, which was first identified in rat as a marker of neuronal differentiation [35], contains a C-terminal stathmin-like domain and a specific N-terminal domain which might be responsible for the membrane association of SCGlO [36]. The other stathmin-related sequence was previously identified as the XB3 cDNA in Xencyus [34]. As SCGIO, the corresponding mRNA was detected exclusively in the nervous system, and its sequence revealed a similar structural organization of the corresponding protein. KeywordsThe existence of SCGIO and XB3 sequences containing a stathmin-like domain, as well as the previously recognized similar intron/exon structure of S...

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Section: Discussionmentioning

confidence: 95%

Section: Rb3/rb3' C a C T C C T T G T G A C T T T T G G T C A A T T Cmentioning

confidence: 99%

The Stathmin Family

Ozon

Maucuer

Sobel

1997

European Journal of Biochemistry

111

102

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“…22,30,31 In the present study, we assessed both the trafficking and cellular distribution of SCG10 in HSCs. To detect endogenous SCG10, we used an existing antibody for SCG10 which was highly specific in Western blot and immunofluorescence.…”

Section: In Situ Localization Of Scg10 and The Trafficking Pathway Inmentioning

confidence: 99%

SCG10 Expression on Activation of Hepatic Stellate Cells Promotes Cell Motility Through Interference with Microtubules

Paradis

Dargère

Bieche

et al. 2010

The American Journal of Pathology

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During liver fibrogenesis , quiescent hepatic stellate cells switch their phenotype toward a myofibroblastic-like pattern with a gain in motility. Here , we show that SCG10 (superior cervical ganglia 10) mRNA expression , a microtubule-destabilizing protein that favors cell growth and motility in neurons , both increases and correlates with the stage of fibrosis in patients with chronic hepatitis C. We also show the de novo expression of SCG10 mRNA in two rat models of liver fibrosis. We demonstrate that activated hepatic stellate cells appear to be the major cellular sources of SCG10 in the liver. Tracking of the SCG10 pathway in hepatic stellate cells shows that SCG10 initially accumulates in the perinuclear Golgi area then migrates in small vesicle-like structures along individual microtubules. Moreover , SCG10 vesicles cluster at the distal ends of microtubules in areas where tubules are spread and decompacted , suggesting their preferential association with destabilized and dynamic microtubules. Inhibition of SCG10 expression by gene-specific short interfering RNA in primary rat hepatic stellate cells is associated with a significant reduction in microtubule-dependent cellular functions , such as proliferation and migration. In conclusion , the de novo expression of SCG10 by hepatic stellate cells may play a major role in cellular mechanisms associated with HSC activation, namely cell motility and division, through interference with microtubules. SCG10 may represent a potential molecular target for antifibrosis therapies.

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“…The N-terminal region of SCG10 (amino acids 1-34) was thought to be important for membrane association, and the removal of this region re-http://bmbreports.org sulted in a soluble protein (∆SCG10) that is closely homologous to conventional stathmin (9). Thus, an N-terminal truncated GST-tagged form of ∆SCG10 was constructed to facilitate the purification of SCG10.…”

Section: Bri3 and Scg10 Associate In Vitro And In Vivomentioning

confidence: 99%

“…SCG10 is a microtubule-destabilizing protein that induces microtubule depolymerization in vitro and when overexpressed in cultured cells (9,12).…”

Section: Effects Of Bri3 and Scg10 Co-expression On Microtubule Organmentioning

confidence: 99%

Targeting of SCG10 to the Area of the Golgi Complex Is Mediated by Its NH2-terminal Region

Cited by 92 publications

References 32 publications

The Stathmin Family

The Stathmin Family

SCG10 Expression on Activation of Hepatic Stellate Cells Promotes Cell Motility Through Interference with Microtubules

BRI₃ associates with SCG10 and attenuates NGF-induced neurite outgrowth in PC12 cells

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Targeting of SCG10 to the Area of the Golgi Complex Is Mediated by Its NH2-terminal Region

Cited by 92 publications

References 32 publications

The Stathmin Family

The Stathmin Family

SCG10 Expression on Activation of Hepatic Stellate Cells Promotes Cell Motility Through Interference with Microtubules

BRI3 associates with SCG10 and attenuates NGF-induced neurite outgrowth in PC12 cells

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BRI₃ associates with SCG10 and attenuates NGF-induced neurite outgrowth in PC12 cells