Abstract：
:Autosomal dominant polycystic kidney disease (ADPKD) is the most common monogenic human disease, with around 12.5 million people affected worldwide. ADPKD results from mutations in either PKD1 or PKD2, which encode the atypical G-protein coupled receptor polycystin-1 (PC1) and the transient receptor potential channel polycystin-2 (PC2), respectively. Although altered intracellular trafficking of PC1 and PC2 is an underlying feature of ADPKD, the mechanisms which govern vesicular transport of the polycystins through the biosynthetic and endosomal membrane networks remain to be fully elucidated. Here, we describe an interaction between PC2 and retromer, a master controller for the sorting of integral membrane proteins through the endo-lysosomal network. We show that association of PC2 with retromer occurs via a region in the PC2 cytoplasmic amino-terminal domain, independently of the retromer-binding Wiskott-Aldrich syndrome and scar homologue (WASH) complex. Based on observations that retromer preferentially interacts with a trafficking population of PC2, and that ciliary levels of PC1 are reduced upon mutation of key residues required for retromer association in PC2, our data are consistent with the identification of PC2 as a retromer cargo protein.This article has an associated First Person interview with the first author of the paper.
journal_name
J Cell Scijournal_title
Journal of cell scienceauthors
Tilley FC,Gallon M,Luo C,Danson CM,Zhou J,Cullen PJdoi
10.1242/jcs.211342subject
Has Abstractpub_date
2018-06-06 00:00:00issue
11eissn
0021-9533issn
1477-9137pii
jcs.211342journal_volume
131pub_type
杂志文章abstract：:Plectin, a cytolinker protein greater than 500 kDa in size, has an important role as a mechanical stabiliser of cells. It interlinks the various cytoskeletal filament systems and anchors intermediate filaments to peripheral junctional complexes. In addition, there is increasing evidence that plectin acts as a scaffold...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：10.1242/jcs.02891
更新日期：2006-05-01 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：:It has long been established that neuronal growth cone navigation depends on changes in microtubule (MT) and F-actin architecture downstream of guidance cues. However, the mechanisms by which MTs and F-actin are dually coordinated remain a fundamentally unresolved question. Here, we report that the well-characterized ...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：10.1242/jcs.224311
更新日期：2019-04-30 00:00:00
abstract：:The Rho-family proteins make up a major branch of the Ras superfamily of small GTPases. To date, 22 human genes encoding at least 25 proteins have been described. The best known 'classical' members are RhoA, Rac1 and Cdc42. Highly related isoforms of these three proteins have not been studied as intensively, in part b...
journal_title：Journal of cell science
pub_type： 杂志文章,评审
doi：10.1242/jcs.01118
更新日期：2004-03-15 00:00:00
abstract：:Splice variants of certain genes impact on genetic biodiversity in mammals. The tumor suppressor TP53 gene (encoding p53) plays an important role in the regulation of tumorigenesis in hepatocellular carcinoma (HCC). Δ40p53α is a naturally occurring p53 isoform that lacks the N-terminal transactivation domain, yet litt...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：10.1242/jcs.190736
更新日期：2017-02-01 00:00:00
abstract：:The sensory functions of cilia are dependent on the enrichment of cilium-resident proteins. Although it is known that ciliary targeting signals (CTSs) specifically target ciliary proteins to cilia, it is still unclear how CTSs facilitate the entry and retention of cilium-resident proteins at the molecular level. We fo...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：10.1242/jcs.194019
更新日期：2016-10-15 00:00:00
abstract：:Notwithstanding the fact that adult bone marrow cell engraftment to epithelial organs seems a somewhat uncommon event, there is no doubt it does occur, and under appropriate conditions of a strong and positive selection pressure these cells will expand clonally and make a significant contribution to tissue replacement...
journal_title：Journal of cell science
pub_type： 杂志文章,评审
doi：10.1242/jcs.00269
更新日期：2003-02-15 00:00:00
abstract：:We investigated at the electron microscope level the fate of the three intranuclear structures known to accumulate snRNPs, and which correspond to the punctuate immunofluorescent staining pattern (the coiled bodies, the clusters of interchromatin granules and the interchromatin granule-associated zones) after exposure...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：
更新日期：1995-03-01 00:00:00
abstract：:Kindlin-2 is a FERM and PH domain-containing integrin-binding protein that is emerging as an important regulator of integrin activation. How kindlin-2 functions in integrin activation, however, is not known. We report here that kindlin-2 interacts with multiple phosphoinositides, preferentially with phosphatidylinosit...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：10.1242/jcs.076976
更新日期：2011-03-15 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：:The regulation and function of the crucial cell cycle regulator cyclin E (CycE) remains elusive. Unlike other cyclins, CycE can be uniquely controlled by mitochondrial energetics, the exact mechanism being unclear. Using mammalian cells (in vitro) and Drosophila (in vivo) model systems in parallel, we show that CycE c...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：10.1242/jcs.172429
更新日期：2015-11-15 00:00:00
abstract：:The endoplasmic reticulum-Golgi intermediate compartment (ERGIC) defined by the cycling lectin ERGIC-53 consists of tubulovesicular clusters, but it is unknown if these membranes are transport vehicles or stationary entities. Here, we show by live imaging that GFP-ERGIC-53 mainly localizes to long-lived stationary and...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：10.1242/jcs.01615
更新日期：2005-01-15 00:00:00
abstract：:Cytidine triphosphate synthase (CTPS) and inosine monophosphate dehydrogenase (IMPDH) (both of which have two isoforms) can form fiber-like subcellular structures termed 'cytoophidia' under certain circumstances in mammalian cells. Although it has been shown that filamentation of CTPS downregulates its activity by dis...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：10.1242/jcs.175265
更新日期：2015-10-01 00:00:00
abstract：:Keratins 8 and 18 (K8 and K18) are regulated by site-specific phosphorylation in response to multiple stresses. We examined the effect and regulation of hyposmotic stress on keratin phosphorylation. K8 phospho-Ser431 (Ser431-P) becomes dephosphorylated in HT29 cells, but hyperphosphorylated on other K8 but not K18 sit...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：10.1242/jcs.02861
更新日期：2006-04-01 00:00:00
abstract：:The asparaginyl hydroxylase factor inhibiting HIF-1 (FIH-1) is an important suppressor of hypoxia-inducible factor (HIF) activity. In addition to HIF-α, FIH-1 was previously shown to hydroxylate other substrates within a highly conserved protein interaction domain, termed the ankyrin repeat domain (ARD). However, to d...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：10.1242/jcs.117564
更新日期：2013-06-15 00:00:00
abstract：:The water pipes of elongating plant organs are the result of programmed cell death and are formed by the walls of dead and empty protoxylem elements. These protoxylem elements are passively elongated many times by the surrounding tissue before they are replaced and collapse. Well-known adaptations for this unique task...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：10.1242/jcs.00966
更新日期：2004-03-01 00:00:00
abstract：:Previous investigators have examined mitochondrial DNA (mtDNA) in the electron microscope (EM) after extraction from mitochondria and rotary shadowing. We have observed mtDNA in situ by the osmiumammine procedure for specific staining of DNA in the EM. The procedure was modified to improve the regularity of the staini...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：
更新日期：1992-04-01 00:00:00
abstract：:Effective cell-to-cell spreading of the facultative intracellular pathogen Listeria monocytogenes requires the interaction between bacteria and the microfilament system of the host cell. By recruiting actin filaments into a 'comet tail' localized at one pole of the bacterial cell wall, Listeria become mobile and prope...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：
更新日期：1994-10-01 00:00:00
abstract：:Cells undergo a variety of physiological processes, including division, migration and differentiation, under the influence of endogenous electrical cues, which are generated physiologically and pathologically in the extracellular and sometimes intracellular spaces. These signals are transduced to regulate cell behavio...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：10.1242/jcs.023564
更新日期：2009-12-01 00:00:00
abstract：:Although membrane addition is crucial for cytokinesis in many animal cell types, the specific mechanisms supporting cleavage furrow ingression are not yet understood. Mutations in the gene brunelleschi (bru), which encodes the Drosophila ortholog of the yeast Trs120p subunit of TRAPPII, cause failure of furrow ingress...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：10.1242/jcs.054536
更新日期：2009-12-15 00:00:00
abstract：:Cryo-ultramicrotomy and X-ray microanalysis were used to study the elemental composition of HeLa S3 cells. Quantitation was achieved by reference to elemental standards of known concentration made up in 25% gelatin. Analysis of standards showed linear calibration for each of the elements studied: Na, P, S, Cl, K. Stan...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：
更新日期：1983-03-01 00:00:00
abstract：:Oocytes of Xenopus laevis in pachytene and early diplotene of meiosis have been studied using the Miller spreading technique. Transcription first appears in germinal vesicles 25-40 micrometers in diameter, when the oocyte is in early diplotene. Transcription at this stage consists of arrays of short RNP transcripts, i...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：
更新日期：1980-08-01 00:00:00
abstract：:Collapsin response mediator proteins (CRMPs) mediate signal transduction of neurite outgrowth and axonal guidance during neuronal development. Voltage-gated Ca(2+) channels and interacting proteins are essential in neuronal signaling and synaptic transmission during this period. We recently identified the presynaptic ...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：10.1242/jcs.053280
更新日期：2009-12-01 00:00:00
abstract：:The functions of polycomb products extend beyond their well-known activity as transcriptional regulators to include genome duplication processes. Polycomb activities during DNA replication and DNA damage repair are unclear, particularly without induced replicative stress. We have used a cellular model of conditionally...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：10.1242/jcs.173021
更新日期：2015-10-01 00:00:00
abstract：:The semaphorin family comprises soluble and membrane-bound proteins originally identified as axonal guidance cues that function during neuronal development. Emerging evidence suggests that a subset of semaphorins, called 'immune semaphorins', function in the immune system. The class IV semaphorins Sema4D/CD100 and Sem...
journal_title：Journal of cell science
pub_type： 杂志文章,评审
doi：10.1242/jcs.00674
更新日期：2003-09-01 00:00:00
abstract：:The movement of cells in small groups, or clusters, was studied in vitro using epithelioid cells from Gordon-Kosswig melanomas (from poecelid fish) and time-lapse cinemicrography. Tumour explants cultured on glass yield cell sheets from which groups of cells separate and become independently motile clusters. These clu...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：
更新日期：1981-06-01 00:00:00
abstract：:In neutrophils and other phagocytic cells, the small GTPase Rac is an essential regulator of a multi-component NADPH oxidase that produces high levels of superoxide, which kills invading pathogens. In many other cell types, Rac and newly discovered relatives of the neutrophil burst oxidase and its subunits have been f...
journal_title：Journal of cell science
pub_type： 杂志文章,评审
doi：10.1242/jcs.00937
更新日期：2004-01-15 00:00:00
abstract：:Maturation of nociceptive neurons depends on changes in transcription factors, ion channels and neuropeptides. Mature nociceptors initiate pain in part by drastically reducing the activation threshold via intracellular sensitization signaling. Whether sensitization signaling also changes during development and aging r...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：10.1242/jcs.197327
更新日期：2017-07-01 00:00:00
abstract：:Using a novel PCR approach, we have cloned a cDNA encoding the entire high molecular weight tau molecule from rat dorsal root ganglia. The resulting 2080 bp cDNA differs from low molecular weight rat brain tau by the insertion of a novel 762 bp region (exon 4a) between exons 4 and 5. This cDNA clone is identical in se...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：
更新日期：1993-07-01 00:00:00
abstract：:The neural cell adhesion molecule NCAM plays an important role during neural development and in the adult brain. To study the intracellular trafficking of NCAM in neurons, two major isoforms, NCAM140 or NCAM180, were expressed in primary cortical neurons and in the rat B35 neuroblastoma cell line. NCAM was endocytosed...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：10.1242/jcs.019729
更新日期：2007-11-15 00:00:00
