Abstract：
:The planar cell polarity (PCP) signalling pathway is essential for embryonic development because it governs diverse cellular behaviours, and 'core PCP' proteins, such as Dishevelled and Frizzled, have been extensively characterized. By contrast, the 'PCP effector' proteins, such as Intu and Fuz, remain largely unstudied. These proteins are essential for PCP signalling, but they have never been investigated in mammals and their cell biological activities remain entirely unknown. We report here that Fuz mutant mice show neural tube defects, skeletal dysmorphologies and Hedgehog signalling defects stemming from disrupted ciliogenesis. Using bioinformatics and imaging of an in vivo mucociliary epithelium, we established a central role for Fuz in membrane trafficking, showing that Fuz is essential for trafficking of cargo to basal bodies and to the apical tips of cilia. Fuz is also essential for exocytosis in secretory cells. Finally, we identified a Rab-related small GTPase as a Fuz interaction partner that is also essential for ciliogenesis and secretion. These results are significant because they provide new insights into the mechanisms by which developmental regulatory systems such as PCP signalling interface with fundamental cellular systems such as the vesicle trafficking machinery.
journal_name
Nat Cell Bioljournal_title
Nature cell biologyauthors
Gray RS,Abitua PB,Wlodarczyk BJ,Szabo-Rogers HL,Blanchard O,Lee I,Weiss GS,Liu KJ,Marcotte EM,Wallingford JB,Finnell RHdoi
10.1038/ncb1966subject
Has Abstractpub_date
2009-10-01 00:00:00pages
1225-32issue
10eissn
1465-7392issn
1476-4679pii
ncb1966journal_volume
11pub_type
杂志文章abstract：:Clathrin-coated vesicles mediate endocytosis and transport between the trans-Golgi network (TGN) and endosomes in eukaryotic cells. Clathrin adaptors play central roles in coat assembly, interacting with clathrin, cargo and membranes. Two main types of clathrin adaptor act in TGN-endosome traffic: GGA proteins and the...
journal_title：Nature cell biology
pub_type： 杂志文章
doi：10.1038/ncb2427
更新日期：2012-02-19 00:00:00
abstract：:The most dangerous insults to the genome's integrity are those that break both strands of the DNA. Double-strand breaks can be repaired by homologous recombination; in this conserved mechanism, a global genomic homology search finds sequences similar to those near the break, and uses them as a template for DNA synthes...
journal_title：Nature cell biology
pub_type： 杂志文章
doi：10.1038/ncb2745
更新日期：2013-06-01 00:00:00
abstract：:Mouse embryos with a loss-of-function mutation in the gene encoding the receptor tyrosine kinase ErbB4 exhibit misprojections of cranial sensory ganglion afferent axons. Here we analyse ErbB4-deficient mice, and find that morphological differences between wild-type and mutant cranial ganglia correlate with aberrant mi...
journal_title：Nature cell biology
pub_type： 杂志文章
doi：10.1038/35000058
更新日期：2000-02-01 00:00:00
abstract：:Protein substrates of the proteasome must apparently be unfolded and translocated through a narrow channel to gain access to the proteolytic active sites of the enzyme. Protein folding in vivo is mediated by molecular chaperones. Here, to test for chaperone activity of the proteasome, we assay the reactivation of dena...
journal_title：Nature cell biology
pub_type： 杂志文章
doi：10.1038/12043
更新日期：1999-08-01 00:00:00
abstract：:Coordination of microtubules and the actin cytoskeleton is important in several types of cell movement. mDia1 is a member of the formin-homology family of proteins and an effector of the small GTPase Rho. It contains the Rho-binding domain in its amino terminus and two distinct regions of formin homology, FH1 in the m...
journal_title：Nature cell biology
pub_type： 杂志文章
doi：10.1038/35050598
更新日期：2001-01-01 00:00:00
abstract：:Hippo signalling has been associated with many important tissue functions including the regulation of organ size. In the intestinal epithelium differing functions have been proposed for the effectors of Hippo signalling, YAP and TAZ1. These are now shown to have a dual role in the intestinal epithelium, regulating bot...
journal_title：Nature cell biology
pub_type： 评论,杂志文章
doi：10.1038/ncb3086
更新日期：2015-01-01 00:00:00
abstract：:SLC7A11-mediated cystine uptake is critical for maintaining redox balance and cell survival. Here we show that this comes at a significant cost for cancer cells with high levels of SLC7A11. Actively importing cystine is potentially toxic due to its low solubility, forcing cancer cells with high levels of SLC7A11 (SLC7...
journal_title：Nature cell biology
pub_type： 杂志文章
doi：10.1038/s41556-020-0496-x
更新日期：2020-04-01 00:00:00
abstract：:KLF4 (GKLF/EZF) encodes a transcription factor that is associated with both tumour suppression and oncogenesis. We describe the identification of KLF4 in a functional genomic screen for genes that bypass RAS(V12)-induced senescence. However, in untransformed cells, KLF4 acts as a potent inhibitor of proliferation. KLF...
journal_title：Nature cell biology
pub_type： 杂志文章
doi：10.1038/ncb1314
更新日期：2005-11-01 00:00:00
abstract：:Cohesin confers both intrachromatid and interchromatid cohesion through formation of a tripartite ring within which DNA is thought to be entrapped. Here, I discuss what is known about the four stages of the cohesin ring cycle using the ring model as an intellectual framework. I postulate that cohesin loading onto chro...
journal_title：Nature cell biology
pub_type： 杂志文章,评审
doi：10.1038/ncb2349
更新日期：2011-10-03 00:00:00
abstract：:Extracellular signal regulated kinases (ERKs) represent a signalling hub in many physiological responses and have pivotal functions in cell proliferation, differentiation, development and death, as well as in synaptic plasticity. Mitogen-activated protein kinase phosphatases (MKPs) selectively inactivate ERKs by depho...
journal_title：Nature cell biology
pub_type： 杂志文章
doi：10.1038/ncb1447
更新日期：2006-08-01 00:00:00
abstract：:Somatic cell reprogramming by exogenous factors requires cooperation with transcriptional co-activators and co-repressors to effectively remodel the epigenetic environment. How this interplay is regulated remains poorly understood. Here, we demonstrate that NCoR/SMRT co-repressors bind to pluripotency loci to create a...
journal_title：Nature cell biology
pub_type： 杂志文章
doi：10.1038/s41556-018-0047-x
更新日期：2018-04-01 00:00:00
abstract：:The ability of exosomes to transfer cargo from donor to acceptor cells, thereby triggering phenotypic changes in the latter, has generated substantial interest in the scientific community. However, the extent to which exosomes differ from other extracellular vesicles in terms of their biogenesis and functions remains ...
journal_title：Nature cell biology
pub_type： 杂志文章,评审
doi：10.1038/s41556-018-0250-9
更新日期：2019-01-01 00:00:00
abstract：:The mitochondrial inner membrane is the central energy-converting membrane of eukaryotic cells. The electrochemical proton gradient generated by the respiratory chain drives the ATP synthase. To maintain this proton-motive force, the inner membrane forms a tight barrier and strictly controls the translocation of ions....
journal_title：Nature cell biology
pub_type： 杂志文章
doi：10.1038/ncb1635
更新日期：2007-10-01 00:00:00
abstract：:Chromosome missegregation into a micronucleus can cause complex and localized genomic rearrangements known as chromothripsis, but the underlying mechanisms remain unresolved. Here we developed an inducible Y centromere-selective inactivation strategy by exploiting a CENP-A/histone H3 chimaera to directly examine the f...
journal_title：Nature cell biology
pub_type： 杂志文章
doi：10.1038/ncb3450
更新日期：2017-01-01 00:00:00
abstract：:Bcl-2 stimulates mutagenesis after the exposure of cells to DNA-damaging agents. However, the biological mechanisms of Bcl-2-mediated mutagenesis have remained largely obscure. Here we demonstrate that the Bcl-2-mediated suppression of hMSH2 expression results in a reduced cellular capacity to repair mismatches. The p...
journal_title：Nature cell biology
pub_type： 杂志文章
doi：10.1038/ncb1215
更新日期：2005-02-01 00:00:00
abstract：:Protein ubiquitination regulates many cellular processes, including protein degradation, signal transduction, DNA repair and cell division. In the classical model, a uniform polyubiquitin chain that is linked through Lys 48 is required for recognition and degradation by the 26S proteasome. Here, we used a reconstitute...
journal_title：Nature cell biology
pub_type： 杂志文章
doi：10.1038/ncb1436
更新日期：2006-07-01 00:00:00
abstract：:Current models for the export of messenger RNA share the notion that the highly abundant class of nuclear RNA-binding proteins--the hnRNP proteins--have a key role in exporting RNA. But recent studies have led to a new understanding of several non-hnRNP proteins, including SR proteins and the conserved mRNA export fac...
journal_title：Nature cell biology
pub_type： 杂志文章,评审
doi：10.1038/ncb0901-e201
更新日期：2001-09-01 00:00:00
abstract：:The function and regulation of repetitive DNA, the 'dark matter' of the genome, is still only rudimentarily understood. Now a study investigating DNA replication of repetitive centromeric chromosome segments has started to expose a fascinating replication program that involves suppression of ATR signalling, in particu...
journal_title：Nature cell biology
pub_type： 评论,杂志文章
doi：10.1038/ncb3367
更新日期：2016-05-27 00:00:00
abstract：:The double fertilization process in angiosperms is based on the delivery of a pair of sperm cells by the pollen tube (the male gametophyte), which elongates towards an embryo sac (the female gametophyte) enclosing an egg and a central cell. Several studies have described the mechanisms of gametophyte interaction, and ...
journal_title：Nature cell biology
pub_type： 杂志文章
doi：10.1038/ncb1345
更新日期：2006-01-01 00:00:00
abstract：:Re-establishment of nuclear structure and chromatin organization after cell division is integral for genome regulation or development and is frequently altered during cancer progression. The mechanisms underlying chromatin expansion in daughter cells remain largely unclear. Here, we describe the transient formation of...
journal_title：Nature cell biology
pub_type： 杂志文章
doi：10.1038/ncb3641
更新日期：2017-12-01 00:00:00
abstract：:Tumour growth and invasiveness require extracellular matrix (ECM) degradation and are stimulated by the GALA pathway, which induces protein O-glycosylation in the endoplasmic reticulum (ER). ECM degradation requires metalloproteases, but whether other enzymes are required is unclear. Here, we show that GALA induces th...
journal_title：Nature cell biology
pub_type： 杂志文章
doi：10.1038/s41556-020-00590-w
更新日期：2020-11-01 00:00:00
abstract：:Chromophore-assisted laser inactivation (CALI) is a light-mediated technique used to selectively inactivate proteins within cells. Here, we demonstrate that GFP can be used as a CALI reagent to locally inactivate proteins in living cells. We show that focused laser irradiation of EGFP-alpha-actinin expressed in Swiss ...
journal_title：Nature cell biology
pub_type： 杂志文章
doi：10.1038/ncb772
更新日期：2002-04-01 00:00:00
abstract：:LATS (large tumour suppressor) is a family of conserved tumour suppressors identified in Drosophila and mammals. Here we show that human LATS1 binds to LIMK1 in vitro and in vivo and colocalizes with LIMK1 at the actomyosin contractile ring during cytokinesis. LATS1 inhibits both the phosphorylation of cofilin by LIMK...
journal_title：Nature cell biology
pub_type： 杂志文章
doi：10.1038/ncb1140
更新日期：2004-07-01 00:00:00
abstract：:Micronucleation of missegregated chromatin can lead to substantial chromosome rearrangements via chromothripsis. However, the molecular details of micronucleus-based chromothripsis are still unclear. Now, an elegant system that specifically induces missegregation of the Y chromosome provides insight into this process,...
journal_title：Nature cell biology
pub_type： 杂志文章
doi：10.1038/ncb3458
更新日期：2016-12-23 00:00:00
abstract：:Lamina-associated polypeptide (LAP) 2alpha is a chromatin-associated protein that binds A-type lamins. Mutations in both LAP2alpha and A-type lamins are linked to human diseases called laminopathies, but the molecular mechanisms are poorly understood. The A-type lamin-LAP2alpha complex interacts with and regulates ret...
journal_title：Nature cell biology
pub_type： 杂志文章
doi：10.1038/ncb1793
更新日期：2008-11-01 00:00:00
abstract：:Examination of the tumour suppressor adenomatous polyposis coli (APC) has shown that it may be multifunctional. Recent work has demonstrated dynamic interactions of APC with the microtubule cytoskeleton, supporting the idea that APC has an important function in cell migration. ...
journal_title：Nature cell biology
pub_type： 新闻,评审
doi：10.1038/35008685
更新日期：2000-04-01 00:00:00
abstract：:The tumour stroma is an active participant during cancer progression. Stromal cells promote tumour progression and metastasis through multiple mechanisms including enhancing tumour invasiveness and angiogenesis, and suppressing immune surveillance. We report here that miR-126/miR-126(*), a microRNA pair derived from a...
journal_title：Nature cell biology
pub_type： 杂志文章
doi：10.1038/ncb2690
更新日期：2013-03-01 00:00:00
abstract：:In three-dimensional matrices cancer cells move with a rounded, amoeboid morphology that is controlled by ROCK-dependent contraction of acto-myosin. In this study, we show that PDK1 is required for phosphorylation of myosin light chain and cell motility, both on deformable gels and in vivo. Depletion of PDK1 alters th...
journal_title：Nature cell biology
pub_type： 杂志文章
doi：10.1038/ncb1675
更新日期：2008-02-01 00:00:00
abstract：:The initial differential treatment of the two X chromosomes during X-chromosome inactivation is controlled by the X-inactivation centre (Xic). This locus determines how many X chromosomes are present in a cell ('counting') and which X chromosome will be inactivated in female cells ('choice'). Critical control sequence...
journal_title：Nature cell biology
pub_type： 杂志文章
doi：10.1038/ncb1365
更新日期：2006-03-01 00:00:00
abstract：:Research on genome stability and integrity now extends far beyond the biochemistry of DNA repair to encompass signal transduction pathways that span numerous aspects of cellular life. Derailed genomic integrity pathways can result in debilitating genetic disorders, premature ageing, predisposition to cancer and degene...
journal_title：Nature cell biology
pub_type：
doi：10.1038/ncb1004-923
更新日期：2004-10-01 00:00:00
