Abstract：
:The Down syndrome critical region (DSCR) on Chromosome 21 contains many genes whose duplication may lead to the major phenotypic features of Down syndrome and especially the associated mental retardation. However, the functions of DSCR genes are mostly unknown and their possible involvement in key brain developmental events still largely unexplored. In this report we show that the protein TTC3, encoded by one of the main DSCR candidate genes, physically interacts with Citron kinase (CIT-K) and Citron N (CIT-N), two effectors of the RhoA small GTPase that have previously been involved in neuronal proliferation and differentiation. More importantly, we found that TTC3 levels can strongly affect the NGF-induced differentiation of PC12 cells, by a CIT-K-dependent mechanism. Indeed, TTC3 overexpression leads to strong inhibition of neurite extension, which can be reverted by CIT-K RNAi. Conversely, TTC3 knockdown stimulates neurite extension in the same cells. Finally, we find that Rho, but not Rho kinase, is required for TTC3 differentiation-inhibiting activity. Our results suggest that the TTC3-RhoA-CIT-K pathway could be a crucial determinant of in vivo neuronal development, whose hyperactivity may result in detrimental effects on the normal differentiation program.
journal_name
J Cell Scijournal_title
Journal of cell scienceauthors
Berto G,Camera P,Fusco C,Imarisio S,Ambrogio C,Chiarle R,Silengo L,Di Cunto Fdoi
10.1242/jcs.000703subject
Has Abstractpub_date
2007-06-01 00:00:00pages
1859-67issue
Pt 11eissn
0021-9533issn
1477-9137pii
jcs.000703journal_volume
120pub_type
杂志文章abstract：:During development, general body plan information must be translated into distinct morphologies of individual cells. Shaping cells is thought to involve cortical cytoskeletal components and Bin-Amphiphysin-Rvs167 (BAR) superfamily proteins. We therefore conducted comprehensive side-by-side loss-of-function studies of ...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：10.1242/jcs.111674
更新日期：2013-01-01 00:00:00
abstract：:Cyclic AMP-dependent protein kinase (cAPK) is the intracellular mediator of signal transduction events involving the adenylate cyclase-cyclic AMP system. A monoclonal antibody (MAb BB1) to the type II regulatory subunit (RII) of cAPK was used in a post-embedding immunogold-labeling procedure to determine the ultrastru...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：
更新日期：1989-08-01 00:00:00
abstract：:We previously reported that the FLA10 locus on the uni linkage group of Chlamydomonas encodes a kinesin homologous protein, KHP1. The fla10 phenotype, which is a temperature-sensitive defect for flagellar assembly and maintenance, is rescued by transformation with the wild-type KHP1 gene. In the present study we ident...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：
更新日期：1996-03-01 00:00:00
abstract：:Addition of lysophosphatidic acid (LPA) to serum-deprived N1E-115 neuronal cells results in rapid f-actin assembly accompanied by neurite retraction and rounding of the cell body due to contraction of the cortical actin cytoskeleton. LPA action is mimicked by activated RhoA, while it is blocked by dominant-negative Rh...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：
更新日期：1997-10-01 00:00:00
abstract：:The specific phosphatase inhibitor okadaic acid (OA) induced fragmentation of the Golgi apparatus in interphase HeLa cells. Immunoelectron microscopy for galactosyltransferase identified a major Golgi fragment composed of a cluster of vesicles and tubules that was morphologically indistinguishable from the 'Golgi clus...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：
更新日期：1991-12-01 00:00:00
abstract：:Fission yeast cells tolerate the total absence of the cdc25 mitotic inducer in two cases, either in cdc2-3w or in wee1 genetic backgrounds. In the cdc2-3w cdc25Delta double mutant, the rate-limiting step leading to mitosis is reaching a critical size. However, the size control of this mutant operates in late G2, which...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：
更新日期：1999-04-01 00:00:00
abstract：:HSP27 and alphaB-crystallin are both members of the small heat shock protein family. alphaB-crystalllin has been proposed to modulate intermediate filaments and recently a mutation in alphaB-crystallin has been identified as the genetic basis of desmin related myopathy. This disease is characterised in its pathology b...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：
更新日期：1999-07-01 00:00:00
abstract：:We have identified a novel autoantibody specificity in scleroderma that we term anti-chromo. These antibodies recognize several chromosomal antigens with apparent molecular mass of between 23 and 25 kDa, as determined by immunoblots. Anti-chromo autoantibodies occur in 10-15% of sera from patients with anti-centromere...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：
更新日期：1993-02-01 00:00:00
abstract：:We have identified a liver-regulating protein involved in cell contact-mediated regulation of Sertoli cell function by primary spermatocytes in rat testis. Liver-regulating protein was studied using monoclonal antibody L8 prepared from rat primitive biliary epithelial cells. This molecule was located in vivo at the in...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：
更新日期：1995-03-01 00:00:00
abstract：:The mixed lineage leukemia (MLL) proto-oncogenic protein is a histone-lysine N-methyltransferase that is produced by proteolytic cleavage and self-association of the respective functionally distinct subunits (MLL(N) and MLL(C)) to form a holocomplex involved in epigenetic transcriptional regulation. On the basis of st...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：10.1242/jcs.080523
更新日期：2011-07-01 00:00:00
abstract：:Mesenchymal stem cells (MSCs) are among the most promising and suitable stem cell types for vascular tissue engineering. Substantial effort has been made to differentiate MSCs towards vascular cell phenotypes, including endothelial cells and smooth muscle cells (SMCs). The microenvironment of vascular cells not only c...
journal_title：Journal of cell science
pub_type： 杂志文章,评审
doi：10.1242/jcs.167783
更新日期：2015-07-15 00:00:00
abstract：:The 26S proteasome is the primary protease responsible for degrading misfolded membrane proteins in the endoplasmic reticulum. Here we examine the specific role of beta subunit function on polypeptide cleavage and membrane release of CFTR, a prototypical ER-associated degradation substrate with 12 transmembrane segmen...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：10.1242/jcs.02732
更新日期：2006-01-15 00:00:00
abstract：:We have investigated the intracellular distribution of insoluble fibronectin in HeLa tumour cells. By indirect immunofluorescence microscopy fibronectin was detected in the nuclear region, but not in the region of the cell surface. Isolated nuclei and isolated nuclear matrices also stained for fibronectin. By quantita...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：
更新日期：1988-03-01 00:00:00
abstract：:Dyneins are motor proteins that move along microtubules. They have many roles in the cell. They drive the beating of cilia and flagella, move cargos in the cytoplasm and function in the mitotic spindle. Dyneins are large and complex protein machines. Until recently, the way they move was poorly understood. In 2012, tw...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：10.1242/jcs.120725
更新日期：2013-02-01 00:00:00
abstract：:Endothelial barrier dysfunction leads to edema and vascular leak, causing high morbidity and mortality. Previously, Abl kinase inhibition has been shown to protect against vascular leak. Using the distinct inhibitory profiles of clinically available Abl kinase inhibitors, we aimed to provide a mechanistic basis for no...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：10.1242/jcs.240077
更新日期：2020-05-14 00:00:00
abstract：:CK2 is a serine/threonine kinase with many substrates, largely unknown modes of regulation and essential roles in mitotic progression. CK2α, a catalytic subunit of CK2, is phosphorylated in mitosis, and here we examine the effect of phosphorylation on CK2α localization. Using phosphospecific antibodies, we show that C...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：10.1242/jcs.077446
更新日期：2011-07-15 00:00:00
abstract：:The essential function of the T cell receptor (TCR) is to translate the engagement of peptides on the major histocompatibility complex (pMHC) into appropriate intracellular signals through the associated cluster of differentiation 3 (CD3) complex. The spatial organization of the TCR-CD3 complex in the membrane is thou...
journal_title：Journal of cell science
pub_type： 杂志文章,评审
doi：10.1242/jcs.226423
更新日期：2019-02-11 00:00:00
abstract：:Traction forces increase after microtubule depolymerization; however, the signaling mechanisms underlying this, in particular the dependence upon myosin II, remain unclear. We investigated the mechanism of traction force increase after nocodazole-induced microtubule depolymerization by applying traction force microsco...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：10.1242/jcs.090563
更新日期：2011-12-15 00:00:00
abstract：:Postsynaptic neuronal dendrites undergo functional and morphological changes in response to pathologically excessive synaptic activation. Although rapid formation of segmental focal swelling (varicosity) is the most prominent hallmark in such excitotoxic injury, little is known about the pathophysiological function of...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：
更新日期：2001-11-01 00:00:00
abstract：:Anionic phospholipids PI(4,5)P2 and phosphatidylserine (PS) are enriched in the cytosolic leaflet of the plasma membrane where endocytic sites form. In this study, we investigated the roles of PI(4,5)P2 and PS in clathrin-mediated endocytosis (CME) site initiation and vesicle formation in Saccharomyces cerevisiae. Liv...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：10.1242/jcs.115741
更新日期：2012-12-15 00:00:00
abstract：:Cells govern tissue shape by exerting highly regulated forces at sites of matrix adhesion. As the major force-bearing adhesion-receptor protein, integrins have a central role in how cells sense and respond to the mechanics of their surroundings. Recent studies have shown that a key aspect of mechanotransduction is the...
journal_title：Journal of cell science
pub_type： 杂志文章,评审
doi：10.1242/jcs.042127
更新日期：2009-01-15 00:00:00
abstract：:Talin binds to β-integrin tails to activate integrins, regulating cell migration, invasion and metastasis. There are two talin genes, TLN1 and TLN2, encoding talin1 and talin2, respectively. Talin1 regulates focal adhesion dynamics, cell migration and invasion, whereas the biological function of talin2 is not clear an...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：10.1242/jcs.185959
更新日期：2016-10-01 00:00:00
abstract：:Mitotic progression is timely regulated by the accumulation and degradation of A- and B-type cyclins. In plants, there are three classes of A-, and two classes of B-type cyclins, but their specific roles are not known. We have generated transgenic tobacco plants in which the ectopic expression of a plant cyclin B2 gen...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：10.1242/jcs.00250
更新日期：2003-02-01 00:00:00
abstract：:The conventional kinesin motor transports many different cargos to specific locations in neurons. How cargos regulate motor function remains unclear. Here we focus on KIF5, the heavy chain of conventional kinesin, and report that the Kv3 (Shaw) voltage-gated K(+) channel, the only known tetrameric KIF5-binding protein...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：10.1242/jcs.122234
更新日期：2013-05-01 00:00:00
abstract：:Endocytic trafficking is regulated by ubiquitylation (also known as ubiquitination) of cargoes and endocytic machineries. The role of ubiquitylation in lysosomal delivery has been well documented, but its role in the recycling pathway is largely unknown. Here, we report that the ubiquitin (Ub) ligase RFFL regulates ub...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：10.1242/jcs.228007
更新日期：2019-02-07 00:00:00
abstract：:The cell types responsible for osteolysis associated with skeletal metastasis of solid malignancies are unclear. Tumour infiltrating macrophages (TIMs) isolated from primary mammary carcinomas of C3H/Avy mice were cultured on bone slices to assess their ability to resorb bone. After 14 days in co-culture with murine m...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：
更新日期：1992-03-01 00:00:00
abstract：:Intercellular propagation of signals through connexin32-containing gap junctions is of major importance in physiological processes like nerve activity-dependent glucose mobilization in liver parenchymal cells and enzyme secretion from pancreatic acinar cells. In these cells, as in other organs, more than one type of c...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：
更新日期：2000-04-01 00:00:00
abstract：:A number of structural and functional subnuclear compartments have been described, including regions exclusive of chromosomes previously hypothesized to form a reactive nuclear space. We have now explored this accessible nuclear space and interchromosomal nucleoplasmic domains experimentally using Xenopus vimentin eng...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：
更新日期：1998-05-01 00:00:00
abstract：:Tetrahymena thermophila swims by the coordinated beating of hundreds of cilia that cover its body. It has been proposed that the outer arm dyneins of the ciliary axoneme control beat frequency, whereas the inner arm dyneins control waveform. To test the role of one of these inner arms, dynein heavy chain 7 protein (Dy...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：10.1242/jcs.007369
更新日期：2007-09-01 00:00:00
abstract：:Friedreich's ataxia is a recessive neurodegenerative disease due to insufficient expression of the mitochondrial protein frataxin. Although it has been shown that frataxin is involved in the control of intracellular iron metabolism, by interfering with the mitochondrial biosynthesis of proteins with iron/sulphur (Fe/S...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：10.1242/jcs.02516
更新日期：2005-09-01 00:00:00
