Abstract：
:A new aspect of research into the pathogenesis of cystic fibrosis (CF) is a genetics-based search for ;modifier genes' that may affect the severity of CF lung disease. Using an alternative, cell biological approach, we show that ITPK1 should be considered a modifier gene. ITPK1 synthesizes an intracellular signal, inositol (3,4,5,6)-tetrakisphosphate [Ins(3,4,5,6)P4]. A bio-activatable, cell-permeable analogue of Ins(3,4,5,6)P4 inhibited Ca2+-dependent secretion of Cl- from polarized monolayers of immortalized mouse tracheal epithelial cells (MTEs). Analysis by high-pressure liquid chromatography showed endogenous Ins(3,4,5,6)P4 levels in CF MTEs were approximately 60% below those in wild-type MTEs (P<0.03). This adaptation, which improves purinergic activation of Ca2+-dependent Cl- secretion in CF MTEs, was exceptionally specific; there was no effect upon the cellular levels of all the other inositol phosphate signals. Real-time PCR provided the explanation: the level of ITPK1 expression in wild-type MTEs was twice as high as that in CF MTEs (P<0.002). The biological impact of this differential gene expression is amplified by ITPK1 being concentrated at the apical membrane of MTEs, which we discovered following confocal immunofluorescence microscopy. Compartmentalization of Ins(3,4,5,6)P4 synthesis adjacent to its site of action will enhance its regulatory capacity.
journal_name
J Cell Scijournal_title
Journal of cell scienceauthors
Yang L,Reece J,Gabriel SE,Shears SBdoi
10.1242/jcs.02836keywords:
subject
Has Abstractpub_date
2006-04-01 00:00:00pages
1320-8issue
Pt 7eissn
0021-9533issn
1477-9137pii
jcs.02836journal_volume
119pub_type
杂志文章abstract：:The possible involvement of osmotically generated hydrostatic pressure in driving actin-rich extensions of the cell surface was examined using cultures of chick neurons. Estimation of the excess internal osmotic pressure of chick neural tissue by vapor pressure deficit osmometry, and of the excess internal hydrostatic...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：
更新日期：1991-04-01 00:00:00
abstract：:The cornified cell envelope (CE), a structure formed in the outermost layers of stratified squamous epithelia, provides a physical barrier against environmental insults. It is composed of several structural proteins, which are irreversibly crosslinked by calcium-activated transglutaminases. The small proline rich prot...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：
更新日期：2001-11-01 00:00:00
abstract：:PACSIN2, a membrane-sculpting BAR domain protein, localizes to caveolae. Here, we found that protein kinase C (PKC) phosphorylates PACSIN2 at serine 313, thereby decreasing its membrane binding and tubulation capacities. Concomitantly, phosphorylation decreased the time span for which caveolae could be tracked at the ...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：10.1242/jcs.167775
更新日期：2015-08-01 00:00:00
abstract：:Nascent transcripts in permeabilized HeLa cells were elongated by approximately 30-2,000 nucleotides in Br-UTP or biotin-14-CTP, before incorporation sites were immunolabelled either pre- or post-embedding, and visualized by light or electron microscopy. Analogues were concentrated in approximately 2,100 (range 2,000-...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：
更新日期：1996-06-01 00:00:00
abstract：:The extracellular matrix molecule tenascin-R (TN-R) and the proteoglycans of the lectican family show an overlapping distribution in the developing brain, have been implicated in similar cellular processes and form a complex network of interactions. Previously, we have demonstrated that TN-R induces microprocesses alo...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：10.1242/jcs.03094
更新日期：2006-08-15 00:00:00
abstract：:The family of integrin transmembrane receptors is essential for the normal function of multicellular organisms by facilitating cell-extracellular matrix adhesion. The vitronectin-binding integrin αVβ5 localizes to focal adhesions (FAs) as well as poorly characterized flat clathrin lattices (FCLs). Here, we show that, ...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：10.1242/jcs.221317
更新日期：2018-11-05 00:00:00
abstract：:Postsynaptic density protein 95 (PSD-95/SAP-90) is a palmitoylated membrane-associated guanylate kinase that oligomerizes and clusters ion channels and associated signaling machinery at excitatory synapses in brain. However, the mechanism for PSD-95 oligomerization and its relationship to ion channel clustering remain...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：10.1242/jcs.00617
更新日期：2003-08-01 00:00:00
abstract：:Dynamin, a microtubule-activated GTPase, has recently been identified as the product of the shibire gene in Drosophila. shi(ts) mutants are defective in synaptic vesicle recycling, which leads to rapid and reversible temperature-sensitive paralysis. In the present study, results from RNase protection assays and analys...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：
更新日期：1992-11-01 00:00:00
abstract：:The essential gene noa (CG 3971; also known as Baldspot) encodes a very long chain fatty acid elongase which is most similar to the mammalian elongase ELOVL6. noa is expressed in the nervous system from embryogenesis on, in imaginal discs, the fat body, malpighian tubules and in the gonads of both sexes. Its function ...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：10.1242/jcs.006551
更新日期：2007-08-15 00:00:00
abstract：:Rab GTPases regulate various membrane trafficking pathways but the mechanisms by which GTPase-activating proteins recognise specific Rabs are not clear. Rab8 is involved in controlling several trafficking processes, including the trafficking of transferrin receptor from the early endosome to the recycling endosome. He...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：10.1242/jcs.102327
更新日期：2012-11-01 00:00:00
abstract：:Cyclins control the activities of cyclin-dependent protein kinases (cdks) and hence play a key role in cell cycle regulation. While B-type cyclins associate with p34cdc2 to trigger entry into mitosis, progression through S phase requires cyclin A, presumably in association with p33cdk2. Vertebrate A- and B-type cyclin...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：
更新日期：1993-10-01 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：:Atherosclerosis depends on risk factors such as hyperlipidemia, smoking, hypertension and diabetes. Although these risk factors are relatively constant throughout the arterial circulation, atherosclerotic plaques occur at specific sites where flow patterns are disturbed, with lower overall magnitude and complex change...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：10.1242/jcs.138313
更新日期：2013-11-15 00:00:00
abstract：:Axenically grown cells of D. discoideum Ax-2 harvested in the log phase of growth, cohere rapidly when shaken in phosphate buffer. After 3.5 days in the stationary phase of growth, cells become completely non-cohesive. Although they do not stick to each other, stationary phase cells do stick to both log phase cells an...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：
更新日期：1979-06-01 00:00:00
abstract：:Dystrophin has been proposed to associate with the skeletal muscle membrane by way of a glycoprotein complex that interacts with its C-terminal domains. Transfection of mdx mouse myotubes in culture or myofibres in vivo with recombinant genes encoding human dystrophin deletion mutants shows, however, that not only the...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：
更新日期：1994-06-01 00:00:00
abstract：:Previously, we showed that an integral component of stored mRNP particles in Xenopus oocytes, Xp54, is a DEAD-box RNA helicase with ATP-dependent RNA-unwinding activity. Xp54 belongs to small family of helicases (DDX6) that associate with mRNA molecules encoding proteins required for progress through meiosis. Here we ...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：
更新日期：2002-01-15 00:00:00
abstract：:Our understanding of cells has progressed rapidly in recent years, mainly because of technological advances. Modern technology now allows us to observe molecular processes in living cells with high spatial and temporal resolution. At the same time, we are beginning to compile the molecular parts list of cells. However...
journal_title：Journal of cell science
pub_type： 杂志文章,评审
doi：10.1242/jcs.200295
更新日期：2017-09-01 00:00:00
abstract：:Cells depend on a highly ordered organisation of their content and must develop strategies to maintain the anisotropic distribution of organelles during periods of nutrient shortage. One of these strategies is to solidify the cytoplasm, which was observed in bacteria and yeast cells with acutely interrupted energy pro...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：10.1242/jcs.231688
更新日期：2019-11-08 00:00:00
abstract：:Neurofilaments (NFs) are the major intermediate filaments (IFs) of mature neurons. They play important roles in the structure and function of axons. Recently, two mutations in the neurofilament light (NFL) subunit have been identified in families affected by Charcot-Marie-Tooth (CMT) neuropathy type 2. We have charact...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：10.1242/jcs.00148
更新日期：2002-12-15 00:00:00
abstract：:Different isoforms of non-muscle myosin II have different distributions in vivo, even within individual cells. In order to understand how these different distributions arise, the distribution and dynamics of non-muscle myosins IIA and myosin IIB were examined in cultured cells using immunofluorescence staining and tim...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：
更新日期：1998-08-01 00:00:00
abstract：:How signaling domains form is an important, yet largely unexplored question. Here, we show that ciliary proteins help establish two contiguous, yet distinct cyclic GMP (cGMP) signaling compartments in Caenorhabditis elegans thermosensory AFD neurons. One compartment, a bona fide cilium, is delineated by proteins assoc...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：10.1242/jcs.157610
更新日期：2014-12-15 00:00:00
abstract：:Basement membranes are complex extracellular matrices contributing to the regulation of growth, migration and differentiation of many cell types. However, little is known about the mechanisms regulating the deposition and assembly of basement membrane from its constituents. We have investigated the role of extracellul...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：
更新日期：1991-06-01 00:00:00
abstract：:U937 human promonocytic leukemia cells express PKC isozymes beta 1, beta 2, epsilon and zeta. Indirect immunocytofluorescence using affinity-purified PKC-specific antibodies indicates that each of the endogenous PKC isozymes in U937 cells display a unique compartmentalization within the intact cell. PKC-beta 1 is dist...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：
更新日期：1995-03-01 00:00:00
abstract：:Besides regulating glucose levels, insulin has been reported to participate actively in many other functions, including modulating inflammatory reactions. In this study we investigated how topical insulin application would affect the diabetic wound healing process. We found that the excessive expression of insulin-deg...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：10.1242/jcs.235838
更新日期：2020-10-12 00:00:00
abstract：:Ran is an abundant GTPase of the Ras superfamily that is highly conserved in eukaryotes. In interphase cells, Ran is mainly nuclear and thought to be predominantly GTP-bound, but it is also present in the cytoplasm, probably GDP-bound. This asymmetric distribution plays an important role in directing nucleocytoplasmic...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：
更新日期：1999-07-01 00:00:00
abstract：:Key factors in the adenosine 3',5'-cyclic monophosphate (cyclic AMP) metabolic pathway are two enzymes responsible for its generation and degradation, namely, adenylate cyclase (AC) and phosphodiesterase (PDE). In LD: 12,12 (12 h light, 12 h dark), these enzymes were found to undergo bimodal, circadian variation of ac...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：
更新日期：1991-10-01 00:00:00
abstract：:Cells respond to a wide variety of mechanical stimuli, ranging from thermal molecular agitation to potentially destructive cell swelling caused by osmotic pressure gradients. The cell membrane presents a major target of the external mechanical forces that act upon a cell, and mechanosensitive (MS) ion channels play a ...
journal_title：Journal of cell science
pub_type： 杂志文章,评审
doi：10.1242/jcs.01232
更新日期：2004-05-15 00:00:00
abstract：:It has been demonstrated that proteins covalently conjugated to folic acid may be taken up by cells via endocytosis after binding to a folate binding protein (FBP) in the cell membrane. The proteins taken up in this manner remain catalytically active and they may modify physiological processes occurring in the cytosol...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：
更新日期：1993-09-01 00:00:00
abstract：:The yeast nuclear scaffold has been shown to bind with high affinity to genomic sequences that permit autonomous DNA replication of plasmids (ARS elements). We describe here conditions for the isolation of a histone-free nuclear substructure, the nuclear scaffold, from Saccharomyces cerevisiae. We examine the protein ...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：
更新日期：1990-07-01 00:00:00
abstract：:The monoclonal antibody Bx63 recognizes a centrosomal antigen of Drosophila melanogaster by indirect immunofluorescence and identifies two proteins, with apparent molecular weights of 185 x 10(3) and 66 x 10(3), on Western blots. We have used this antibody to isolate five clones (lambda cs1, -2, -3, -4 and lambda j63)...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：
更新日期：1988-04-01 00:00:00
