Abstract:
:The study of regulated exocytosis uniquely allows the direct measurement of intracellular membrane fusion events in real time. We have exploited this to examine factors that regulate not only the extent but also the dynamics of single fusion/release events. The general strategy used has been to assess exocytosis in transiently transfected PC12 or adrenal chromaffin cells. We aimed to design mutant constructs based on in vitro biochemistry, in some cases informed by knowledge of protein structure. Using this approach we have demonstrated an inhibitory role for the putative Rab3 effector Noc2 that requires interaction with Rab3. Using carbon-fibre amperometry on adrenal chromaffin cells, we have demonstrated regulation of the kinetics of single granule release events consistent with changes in fusion pore dynamics and switches between full fusion and 'kiss-and-run' fusion. These studies have demonstrated a late role for cysteine string protein in exocytosis. In addition, they have focused attention on a key role for Munc18 in the regulation of post-fusion events that affect fusion pore dynamics.
journal_name
Biochem Soc Transjournal_title
Biochemical Society transactionsauthors
Burgoyne RD,Fisher RJ,Graham ME,Haynes LP,Morgan Adoi
10.1042/bst0290467keywords:
subject
Has Abstractpub_date
2001-08-01 00:00:00pages
467-72issue
Pt 4eissn
0300-5127issn
1470-8752journal_volume
29pub_type
杂志文章,评审abstract::MAPK (mitogen-activated protein kinase) signalling pathways contribute to the regulation of diverse responses, including normal and pathological aspects of cell growth, division, differentiation and death. Their ubiquity and versatility raise the issue of how they achieve specific coupling of signal with cellular resp...
journal_title:Biochemical Society transactions
pub_type: 杂志文章
doi:10.1042/BST0340837
更新日期:2006-11-01 00:00:00
abstract::It has long been reported that Mycobacterium tuberculosis is capable of synthesizing the α-glucan glycogen. However, what makes this bacterium stand out is that it coats itself in a capsule that mainly consists of a glycogen-like α-glucan. This polymer helps the pathogen evade immune responses. In 2010, the biosynthes...
journal_title:Biochemical Society transactions
pub_type: 杂志文章,评审
doi:10.1042/BST20150181
更新日期:2016-02-01 00:00:00
abstract::Yeast cells rely on the SPS-sensing pathway to respond to extracellular amino acids. This nutrient-induced signal transduction pathway regulates gene expression by controlling the activity of two redundant transcription factors: Stp1 and Stp2. These factors are synthesized as latent cytoplasmic proteins with N-termina...
journal_title:Biochemical Society transactions
pub_type: 杂志文章,评审
doi:10.1042/BST0370242
更新日期:2009-02-01 00:00:00
abstract::Autophagy is an evolutionarily conserved lysosome-mediated degradation and recycling process, which functions in cellular homeostasis and stress adaptation. The process is highly dynamic and involves autophagosome synthesis, cargo recognition and transport, autophagosome-lysosome fusion, and cargo degradation. The mul...
journal_title:Biochemical Society transactions
pub_type: 杂志文章,评审
doi:10.1042/BST20170102
更新日期:2018-02-19 00:00:00
abstract::The fission yeast Schizosaccharomyces pombe primarily detects glucose via a cAMP-signalling pathway. Components of this pathway include the Git3 G-protein-coupled receptor and a heterotrimeric G-protein, from which the Gpa2 Galpha subunit activates adenylate cyclase (Git2/Cyr1). Three additional proteins, Git1, Git7 a...
journal_title:Biochemical Society transactions
pub_type: 杂志文章,评审
doi:10.1042/BST0330257
更新日期:2005-02-01 00:00:00
abstract::Here, I review three new structural studies from our laboratory. First, the crystal structure of RNA polymerase (Pol) II in complex with an RNA inhibitor revealed that this RNA blocks transcription initiation by preventing DNA loading into the active-centre cleft. Secondly, the structure of the SRI (Set2 Rpb1-interact...
journal_title:Biochemical Society transactions
pub_type: 杂志文章,评审
doi:10.1042/BST0341058
更新日期:2006-12-01 00:00:00
abstract::AD (Alzheimer's disease) is a neurodegenerative disorder characterized by the abnormal hyperphosphorylation and aggregation of the microtubule-associated protein tau and the misfolding and deposition of Abeta peptide. The mechanisms by which tau and Abeta become abnormal is not clearly understood, neither is it known ...
journal_title:Biochemical Society transactions
pub_type: 杂志文章,评审
doi:10.1042/BST0380988
更新日期:2010-08-01 00:00:00
abstract::Molecular bioenergetics deals with the construction, function and regulation of the powerhouses of life. The present overview sketches scenes and actors, farsighted goals and daring hypotheses, meticulous tool-making, painstaking benchwork, lucky discovery, serious scepticism, emphatic believing and strong characters ...
journal_title:Biochemical Society transactions
pub_type: 杂志文章,评审
doi:10.1042/BST20130199
更新日期:2013-10-01 00:00:00
abstract::The examples shown here illustrate the power of gene targeting to the epidermis as a means of developing animal models for the study of human skin diseases. In this short review, I have focused on contributions which stem predominantly from my own laboratory [31, 32, 34, 37, 47]. However, other laboratories have also ...
journal_title:Biochemical Society transactions
pub_type: 杂志文章,评审
doi:10.1042/bst0191112
更新日期:1991-11-01 00:00:00
abstract::Genetic experiments have indicated that succinoglycan (EPS I), the acidic Calcofluor-binding exopolysaccharide, of the nitrogen-fixing bacterium Rhizobium meliloti strain Rm1021 is required for nodule invasion and possibly for later events in nodule development on alfalfa and other hosts. Fourteen exo loci on the seco...
journal_title:Biochemical Society transactions
pub_type: 杂志文章,评审
doi:10.1042/bst0190636
更新日期:1991-08-01 00:00:00
abstract::HD (Huntington's disease) is a late onset heritable neurodegenerative disorder that is characterized by neuronal dysfunction and death, particularly in the cerebral cortex and medium spiny neurons of the striatum. This is followed by progressive chorea, dementia and emotional dysfunction, eventually resulting in death...
journal_title:Biochemical Society transactions
pub_type: 杂志文章,评审
doi:10.1042/BST0371270
更新日期:2009-12-01 00:00:00
abstract::The expression of diacylglycerol acyltransferase (DGAT, EC 2.3.1.20) with predicted molecular mass of 56.9. kDa (BnDGAT1) was examined using microspore-derived cell suspension cultures of oilseed rape (Brassica napus L. cv Jet Neuf). As well, a recombinant histidine-tagged N-terminal fragment of BnDGAT1 [BnDGAT1((1-11...
journal_title:Biochemical Society transactions
pub_type: 杂志文章
doi:
更新日期:2000-12-01 00:00:00
abstract::Mutations in the X-linked MECP2 gene are the primary cause of the severe autism spectrum disorder RTT (Rett syndrome). Deletion of Mecp2 in mice recapitulates many of the overt neurological features seen in humans, and the delayed onset of symptoms is accompanied by deficits in neuronal morphology and synaptic physiol...
journal_title:Biochemical Society transactions
pub_type: 杂志文章,评审
doi:10.1042/BST0380498
更新日期:2010-04-01 00:00:00
abstract::LRRK2 mutation is the most common inherited, autosomal dominant cause of Parkinson's disease (PD) and has also been observed in sporadic cases. Most mutations result in increased LRRK2 kinase activity. LRRK2 is highly expressed in brain regions that receive dense, convergent innervation by dopaminergic and glutamaterg...
journal_title:Biochemical Society transactions
pub_type: 杂志文章,评审
doi:10.1042/BST20180468
更新日期:2018-12-17 00:00:00
abstract::Formin family proteins (formins) represent an evolutionary conserved protein family encoded in the genome of a wide range of eukaryotes. Formins are hallmarked by a formin homology 1 (FH1) domain juxtaposed to an FH2 domain whereby they control actin and microtubule dynamics. Not surprisingly, formins are best known a...
journal_title:Biochemical Society transactions
pub_type: 杂志文章,评审
doi:10.1042/BST20160187
更新日期:2016-12-15 00:00:00
abstract::Abnormal protein aggregation and intracellular or extracellular accumulation of misfolded and aggregated proteins are key events in the pathogenesis of different neurodegenerative diseases. Furthermore, endoplasmic reticulum stress and impairment of the ubiquitin-proteasome system probably contribute to neurodegenerat...
journal_title:Biochemical Society transactions
pub_type: 杂志文章,评审
doi:10.1042/BST0380150
更新日期:2010-02-01 00:00:00
abstract::A new method of monitoring the rate of reactions in solid-phase peptide synthesis is described. A conductivity detector in the reaction cell (patent applied for) enables the deprotection, washing and subsequent coupling stages to be examined in detail. The half-lives of the reactions can be calculated and hence the op...
journal_title:Biochemical Society transactions
pub_type: 杂志文章
doi:10.1042/bst0181308a
更新日期:1990-12-01 00:00:00
abstract::An extraordinary array of P450 (cytochrome P450) enzymes are encoded on the genome of the human pathogen Mycobacterium tuberculosis (Mtb) and in related mycobacteria and actinobacteria. These include the first characterized sterol 14alpha-demethylase P450 (CYP51), a known target for azole and triazole drugs in yeasts ...
journal_title:Biochemical Society transactions
pub_type: 杂志文章,评审
doi:10.1042/BST0341178
更新日期:2006-12-01 00:00:00
abstract::Cystic fibrosis, one of the major human inherited diseases, is caused by defects in the CFTR (cystic fibrosis transmembrane conductance regulator), a cell-membrane protein. CFTR acts as a chloride channel which can be opened by ATP. Low-resolution structural studies of purified recombinant human CFTR are described in ...
journal_title:Biochemical Society transactions
pub_type: 杂志文章
doi:10.1042/BST20050996
更新日期:2005-11-01 00:00:00
abstract::Here, we describe a recently discovered O-GlcNAc transferase termed EOGT for EGF domain-specific O-GlcNAc transferase. EOGT transfers GlcNAc (N-acetylglucosamine) to Ser or Thr in secreted and membrane proteins that contain one or more epidermal growth factor-like repeats with a specific consensus sequence. Thus, EOGT...
journal_title:Biochemical Society transactions
pub_type: 杂志文章,评审
doi:10.1042/BST20160165
更新日期:2017-04-15 00:00:00
abstract::In the present article, I discuss recent developments in the naming of the TOR (target of rapamycin) protein. In particular, I address the issue of mammalian target of rapamycin (mTOR) versus the newer mechanistic target of rapamycin (MTOR). mTOR is the name given by the TOR community almost two decades ago and widely...
journal_title:Biochemical Society transactions
pub_type: 杂志文章
doi:10.1042/BST20130092
更新日期:2013-08-01 00:00:00
abstract::Tetraspanin CD9 is associated with integrin adhesion receptors and it was reported that CD9 regulates integrin-dependent cell migration and invasion. Pro- and anti-migratory effects of CD9 have been linked to adhesion-dependent signalling pathways, including phosphorylation of FAK (focal adhesion kinase) and activatio...
journal_title:Biochemical Society transactions
pub_type: 杂志文章,评审
doi:10.1042/BST0390563
更新日期:2011-04-01 00:00:00
abstract::JAK (Janus kinase) 2 plays a critical role in signal transduction through several cytokine receptors. JAKs contain a typical tyrosine kinase domain preceded by a pseudokinase [JH2 (JAK homology 2)] domain which has been considered to be catalytically inactive. Identification of activating mutations in the JH2 domain o...
journal_title:Biochemical Society transactions
pub_type: 杂志文章,评审
doi:10.1042/BST20130005
更新日期:2013-08-01 00:00:00
abstract::The Drosophila melanogaster flightless I protein and its homologues in higher eukaryotes (FliI) are conserved members of the gelsolin family of actin-binding proteins. Members of the gelsolin family generally contain three or six copies of a 125-amino-acid residue gelsolin-related repeating unit, and may contain addit...
journal_title:Biochemical Society transactions
pub_type: 杂志文章,评审
doi:10.1042/BST0320940
更新日期:2004-12-01 00:00:00
abstract::Tyrosine kinases are signaling molecules that are common to all metazoans and are involved in the regulation of many cellular processes such as proliferation and survival. While most attention has been devoted to tyrosine kinases signaling at the plasma membrane and the cytosol, very little attention has been dedicate...
journal_title:Biochemical Society transactions
pub_type: 杂志文章,评审
doi:10.1042/BST20190543
更新日期:2020-02-28 00:00:00
abstract::Frequent subversion of the PI3K (phosphoinositide 3-kinase) pathway during neoplastic transformation contributes to several hallmarks of cancer that result in a competitive advantage for cancer cells. Deregulation of this pathway can be the result of genomic alterations such as PIK3CA mutation, PTEN (phosphatase and t...
journal_title:Biochemical Society transactions
pub_type: 杂志文章,评审
doi:10.1042/BST20140034
更新日期:2014-08-01 00:00:00
abstract::The discovery of the zDHHC family of S-acyltransferase enzymes has been one of the major breakthroughs in the S-acylation field. Now, more than a decade since their discovery, major questions centre on profiling the substrates of individual zDHHC enzymes (there are 24 ZDHHC genes and several hundred S-acylated protein...
journal_title:Biochemical Society transactions
pub_type: 杂志文章,评审
doi:10.1042/BST20140270
更新日期:2015-04-01 00:00:00
abstract::ATP-binding cassette (ABC) transporters play crucial roles in cellular processes, such as nutrient uptake, drug resistance, cell-volume regulation and others. Despite their importance, all proposed molecular models for transport are based on indirect evidence, i.e. functional interpretation of static crystal structure...
journal_title:Biochemical Society transactions
pub_type: 杂志文章,评审
doi:10.1042/BST20150140
更新日期:2015-10-01 00:00:00
abstract::Starting shortly after parturition, and continuing throughout our lifetime, the gut microbiota coevolves with our metabolic and neurological programming. This symbiosis is regulated by a complex interplay between the host and environmental factors, including diet and lifestyle. Not surprisingly, the development of thi...
journal_title:Biochemical Society transactions
pub_type: 杂志文章
doi:10.1042/BST20191144
更新日期:2020-06-29 00:00:00
abstract::The XMAP215 (Xenopus microtubule-associated protein 215) and CLASP [CLIP-170 (cytoskeletal linker protein 170) associated protein] microtubule plus end tracking families play central roles in the regulation of interphase microtubule dynamics and the proper formation of mitotic spindle architecture and flux. XMAP215 me...
journal_title:Biochemical Society transactions
pub_type: 杂志文章,评审
doi:10.1042/BST0371002
更新日期:2009-10-01 00:00:00