Biochemical Society Symposia最新文献

PLCzeta, a sperm-specific PLC and its potential role in fertilization. PLCzeta，精子特异性PLC及其在受精中的潜在作用。

Biochemical Society Symposia Pub Date : 2007-01-01 DOI: 10.1042/BSS0740023

Christopher M Saunders, Karl Swann, F Anthony Lai

引用次数: 76

Inositol lipids and TRPC channel activation. 肌醇脂和TRPC通道激活。

Biochemical Society Symposia Pub Date : 2007-01-01 DOI: 10.1042/BSS0740037

James W Putney

{"title":"Inositol lipids and TRPC channel activation.","authors":"James W Putney","doi":"10.1042/BSS0740037","DOIUrl":"https://doi.org/10.1042/BSS0740037","url":null,"abstract":"The original hypothesis put forth by Bob Michell in his seminal 1975 review held that inositol lipid breakdown was involved in the activation of plasma membrane calcium channels or 'gates'. Subsequently, it was demonstrated that while the interposition of inositol lipid breakdown upstream of calcium signalling was correct, it was predominantly the release of Ca2+ that was activated, through the formation of Ins(1,4,5)P3. Ca2+ entry across the plasma membrane involved a secondary mechanism signalled in an unknown manner by depletion of intracellular Ca2+ stores. In recent years, however, additional non-store-operated mechanisms for Ca2+ entry have emerged. In many instances, these pathways involve homologues of the Drosophila trp (transient receptor potential) gene. In mammalian systems there are seven members of the TRP superfamily, designated TRPC1-TRPC7, which appear to be reasonably close structural and functional homologues of Drosophila TRP. Although these channels can sometimes function as store-operated channels, in the majority of instances they function as channels more directly linked to phospholipase C activity. Three members of this family, TRPC3, 6 and 7, are activated by the phosphoinositide breakdown product, diacylglycerol. Two others, TRPC4 and 5, are also activated as a consequence of phospholipase C activity, although the precise substrate or product molecules involved are still unclear. Thus the TRPCs represent a family of ion channels that are directly activated by inositol lipid breakdown, confirming Bob Michell's original prediction 30 years ago.","PeriodicalId":55383,"journal":{"name":"Biochemical Society Symposia","volume":" 74","pages":"37-45"},"PeriodicalIF":0.0,"publicationDate":"2007-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"26497912","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 28

Pleckstrin homology (PH) domains and phosphoinositides. Pleckstrin同源结构域与磷酸肌苷。

Biochemical Society Symposia Pub Date : 2007-01-01 DOI: 10.1042/BSS0740081

Mark A Lemmon

{"title":"Pleckstrin homology (PH) domains and phosphoinositides.","authors":"Mark A Lemmon","doi":"10.1042/BSS0740081","DOIUrl":"10.1042/BSS0740081","url":null,"abstract":"PH (pleckstrin homology) domains represent the 11th most common domain in the human proteome. They are best known for their ability to bind phosphoinositides with high affinity and specificity, although it is now clear that less than 10% of all PH domains share this property. Cases in which PH domains bind specific phosphoinositides with high affinity are restricted to those phosphoinositides that have a pair of adjacent phosphates in their inositol headgroup. Those that do not [PtdIns3P, PtdIns5P and PtdIns(3,5)P2] are instead recognized by distinct classes of domains including FYVE domains, PX (phox homology) domains, PHD (plant homeodomain) fingers and the recently identified PROPPINs (b-propellers that bind polyphosphoinositides). Of the 90% of PH domains that do not bind strongly and specifically to phosphoinositides, few are well understood. One group of PH domains appears to bind both phosphoinositides (with little specificity) and Arf (ADP-ribosylation factor) family small G-proteins, and are targeted to the Golgi apparatus where both phosphoinositides and the relevant Arfs are both present. Here, the PH domains may function as coincidence detectors. A central challenge in understanding the majority of PH domains is to establish whether the very low affinity phosphoinositide binding reported in many cases has any functional relevance. For PH domains from dynamin and from Dbl family proteins, this weak binding does appear to be functionally important, although its precise mechanistic role is unclear. In many other cases, it is quite likely that alternative binding partners are more relevant, and that the observed PH domain homology represents conservation of structural fold rather than function.","PeriodicalId":55383,"journal":{"name":"Biochemical Society Symposia","volume":" 74","pages":"81-93"},"PeriodicalIF":0.0,"publicationDate":"2007-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1042/BSS0740081","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"26496597","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 338

Structural studies of phosphoinositide 3-kinase-dependent traffic to multivesicular bodies. 磷酸肌肽3-激酶依赖性多泡体转运的结构研究。

Biochemical Society Symposia Pub Date : 2007-01-01 DOI: 10.1042/BSS0740047

David J Gill, Hsiangling Teo, Ji Sun, Olga Perisic, Dmitry B Veprintsev, Yvonne Vallis, Scott D Emr, Roger L Williams

{"title":"Structural studies of phosphoinositide 3-kinase-dependent traffic to multivesicular bodies.","authors":"David J Gill, Hsiangling Teo, Ji Sun, Olga Perisic, Dmitry B Veprintsev, Yvonne Vallis, Scott D Emr, Roger L Williams","doi":"10.1042/BSS0740047","DOIUrl":"https://doi.org/10.1042/BSS0740047","url":null,"abstract":"Three large protein complexes known as ESCRT I, ESCRT II and ESCRT III drive the progression of ubiquitinated membrane cargo from early endosomes to lysosomes. Several steps in this process critically depend on PtdIns3P, the product of the class III phosphoinositide 3-kinase. Our work has provided insights into the architecture, membrane recruitment and functional interactions of the ESCRT machinery. The fan-shaped ESCRT I core and the trilobal ESCRT II core are essential to forming stable, rigid scaffolds that support additional, flexibly-linked domains, which serve as gripping tools for recognizing elements of the MVB (multivesicular body) pathway: cargo protein, membranes and other MVB proteins. With these additional (non-core) domains, ESCRT I grasps monoubiquitinated membrane proteins and the Vps36 subunit of the downstream ESCRT II complex. The GLUE (GRAM-like, ubiquitin-binding on Eap45) domain extending beyond the core of the ESCRT II complex recognizes PtdIns3P-containing membranes, monoubiquitinated cargo and ESCRT I. The structure of this GLUE domain demonstrates that it has a split PH (pleckstrin homology) domain fold, with a non-typical phosphoinositide-binding pocket. Mutations in the lipid-binding pocket of the ESCRT II GLUE domain cause a strong defect in vacuolar protein sorting in yeast.","PeriodicalId":55383,"journal":{"name":"Biochemical Society Symposia","volume":" 74","pages":"47-57"},"PeriodicalIF":0.0,"publicationDate":"2007-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"26497913","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 15

PtdIns5P: a little phosphoinositide with big functions? PtdIns5P:小功能的磷酸肌肽?

Biochemical Society Symposia Pub Date : 2007-01-01 DOI: 10.1042/BSS0740117

Sophie Coronas, Damien Ramel, Caroline Pendaries, Frédérique Gaits-Iacovoni, Hélène Tronchère, Bernard Payrastre

引用次数: 36

Our FABulous VACation: a decade of phosphatidylinositol 3,5-bisphosphate. 我们的美妙假期:磷脂酰肌醇3,5-二磷酸的十年。

Biochemical Society Symposia Pub Date : 2007-01-01 DOI: 10.1042/BSS0740129

Stephen K Dove, Zoë E Johnson

引用次数: 15

The inositol polyphosphate 5-phosphatases: traffic controllers, waistline watchers and tumour suppressors? 肌醇聚磷酸5-磷酸酶:交通控制者、腰围控制者和肿瘤抑制者?

Biochemical Society Symposia Pub Date : 2007-01-01 DOI: 10.1042/BSS0740161

Megan V Astle, Kristy A Horan, Lisa M Ooms, Christina A Mitchell

引用次数: 59

The IP3 receptor/Ca2+ channel and its cellular function. IP3受体/Ca2+通道及其细胞功能。

Biochemical Society Symposia Pub Date : 2007-01-01 DOI: 10.1042/BSS0740009

Katsuhiko Mikoshiba

{"title":"The IP3 receptor/Ca2+ channel and its cellular function.","authors":"Katsuhiko Mikoshiba","doi":"10.1042/BSS0740009","DOIUrl":"https://doi.org/10.1042/BSS0740009","url":null,"abstract":"The IP3R [IP3 (inositol 1,4,5-trisphosphate) receptor] is responsible for Ca2+ release from the ER (endoplasmic reticulum). We have been working extensively on the P400 protein, which is deficient in Purkinje-neuron-degenerating mutant mice. We have discovered that P400 is an IP3R and we have determined the primary sequence. Purified IP3R, when incorporated into a lipid bilayer, works as a Ca2+ release channel and overexpression of IP3R shows enhanced IP3 binding and channel activity. Addition of an antibody blocks Ca2+ oscillations indicating that IP3R1 works as a Ca2+ oscillator. Studies on the role of IP3R during development show that IP3R is involved in fertilization and is essential for determination of dorso-ventral axis formation. We found that IP3R is involved in neuronal plasticity. A double homozygous mutant of IP3R2 (IP3R type 2) and IP3R3 (IP3R type 3) shows a deficit of saliva secretion and gastric juice secretion suggesting that IP3Rs are essential for exocrine secretion. IP3R has various unique properties: cryo-EM (electron microscopy) studies show that IP3R contains multiple cavities; IP3R allosterically and dynamically changes its form reversibly (square form-windmill form); IP3R is functional even though it is fragmented by proteases into several pieces; the ER forms a meshwork but also forms vesicular ER and moves along microtubules using a kinesin motor; X ray analysis of the crystal structure of the IP3 binding core consists of an N-terminal beta-trefoil domain and a C-terminal alpha-helical domain. We have discovered ERp44 as a redox sensor in the ER which binds to the luminal part of IP3R1 and regulates its activity. We have also found the role of IP3 is not only to release Ca2+ but also to release IRBIT which binds to the IP3 binding core of IP3R.","PeriodicalId":55383,"journal":{"name":"Biochemical Society Symposia","volume":" 74","pages":"9-22"},"PeriodicalIF":0.0,"publicationDate":"2007-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"26497910","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 113

Inositol trisphosphate and calcium oscillations. 肌醇三磷酸和钙振荡。

Biochemical Society Symposia Pub Date : 2007-01-01 DOI: 10.1042/BSS0740001

Michael J Berridge

{"title":"Inositol trisphosphate and calcium oscillations.","authors":"Michael J Berridge","doi":"10.1042/BSS0740001","DOIUrl":"https://doi.org/10.1042/BSS0740001","url":null,"abstract":"InsP3 has two important functions in generating Ca2+ oscillations. It releases Ca2+ from the internal store and it can contribute to Ca2+ entry. A hypothesis has been developed to describe a mechanism for Ca2+ oscillations with particular emphasis on the way agonist concentration regulates oscillator frequency. The main idea is that the InsP3 receptors are sensitized to release Ca2+ periodically by cyclical fluctuations of Ca2+ within the lumen of the endoplasmic reticulum. Each time a pulse of Ca2+ is released, the luminal level of Ca2+ declines and has to be replenished before the InsP3 receptors are resensitized to deliver the next pulse of Ca2+. It is this loading of the internal store that explains why frequency is sensitive to external Ca2+ and may also account for how variations in agonist concentration are translated into changes in oscillation frequency. Variations in agonist-induced entry of external Ca2+, which can occur through different mechanisms, determine the variable rates of store loading responsible for adjusting the sensitivity of the InsP3 receptors to produce the periodic pulses of Ca2+. The Ca2+ oscillator is an effective analogue-to-digital converter in that variations in the concentration of the external stimulus are translated into a change in oscillator frequency.","PeriodicalId":55383,"journal":{"name":"Biochemical Society Symposia","volume":" 74","pages":"1-7"},"PeriodicalIF":0.0,"publicationDate":"2007-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"26497909","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 136

Multiple functions of inositolphosphorylceramides in the formation and intracellular transport of glycosylphosphatidylinositol-anchored proteins in yeast. 酵母中肌醇磷酸化神经酰胺在糖基磷脂酰肌醇锚定蛋白的形成和细胞内转运中的多重功能。

Biochemical Society Symposia Pub Date : 2007-01-01 DOI: 10.1042/BSS0740199

Régine Bosson, Andreas Conzelmann

{"title":"Multiple functions of inositolphosphorylceramides in the formation and intracellular transport of glycosylphosphatidylinositol-anchored proteins in yeast.","authors":"Régine Bosson, Andreas Conzelmann","doi":"10.1042/BSS0740199","DOIUrl":"https://doi.org/10.1042/BSS0740199","url":null,"abstract":"The mature sphingolipids of yeast consist of IPCs (inositolphosphorylceramides) and glycosylated derivatives thereof. Beyond being an abundant membrane constituent in the organelles of the secretory pathway, IPCs are also used to constitute the lipid moiety of the majority of GPI (glycosylphosphatidylinositol) proteins, while a minority of GPI proteins contain PI (phosphatidylinositol). Thus all GPI anchor lipids (as well as free IPCs) typically contain C26 fatty acids. However, the primary GPI lipid that isadded to newly synthesized proteins in the endoplasmic reticulum consists of a PI with conventional C16 and C18 fatty acids. A new class of enzymes is required to replace the fatty acid in sn-2 by a C26 fatty acid. Cells lacking this activity make normal amounts of GPI proteins but accumulate GPI anchors containing lyso-PI. As a consequence, the endoplasmic reticulum to Golgi transport of the GPI protein Gas1p is slow, and mature Gas1p is lost from the plasma membrane into the medium. The GPI anchor containing C26 in sn-2 can further be remodelled by the exchange of diacylglycerol for ceramide. This process is also dependent on the presence of specific phosphorylethanolamine side-chains on the GPI anchor.","PeriodicalId":55383,"journal":{"name":"Biochemical Society Symposia","volume":" 74","pages":"199-209"},"PeriodicalIF":0.0,"publicationDate":"2007-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"26553853","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 9