Inside the cell最新文献

{"title":"Disabled-2: A modular scaffold protein with multifaceted functions in signaling","authors":"Carla V. Finkielstein,&nbsp;Daniel G. S. Capelluto","doi":"10.1002/icl3.1021","DOIUrl":"https://doi.org/10.1002/icl3.1021","url":null,"abstract":"<div>\u0000 <p>Disabled-2 (Dab2) is a multimodular scaffold protein with signaling roles in the domains of cell growth, trafficking, differentiation, and homeostasis. Emerging evidences place Dab2 as a novel modulator of cell–cell interaction; however, its mode of action has remained largely elusive. In this review, we highlight the relevance of Dab2 function in cell signaling and development and provide the most recent and comprehensive analysis of Dab2's action as a mediator of homotypical and heterotypical interactions. Accordingly, Dab-2 controls the extent of platelet aggregation through various motifs within its N-terminus. Dab2 interacts with the cytosolic tail of the integrin receptor blocking <i>inside-out</i> signaling, whereas extracellular Dab2 competes with fibrinogen for integrin α_IIbβ₃ receptor binding and, thus, modulates <i>outside-in</i> signaling. An additional level of regulation results from Dab2's association with cell surface lipids, an event that defines the extent of cell–cell interactions. As a multifaceted regulator, Dab2 acts as a mediator of endocytosis through its association with the [FY]xNPx[YF] motifs of internalized cell surface receptors, phosphoinositides, and clathrin. Other emerging roles of Dab2 include its participation in developmental mechanisms required for tissue formation and in modulation of immune responses. This review highlights the various novel mechanisms by which Dab2 mediates an array of signaling events with vast physiological consequences.</p>\u0000 </div>","PeriodicalId":91499,"journal":{"name":"Inside the cell","volume":"1 1","pages":"48-58"},"PeriodicalIF":0.0,"publicationDate":"2015-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1002/icl3.1021","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"137634316","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}

{"title":"Mitochondrial uncoupling proteins regulate angiotensin-converting enzyme expression: crosstalk between cellular and endocrine metabolic regulators suggested by RNA interference and genetic studies","authors":"Sukhbir S. Dhamrait,&nbsp;Cecilia Maubaret,&nbsp;Ulrik Pedersen-Bjergaard,&nbsp;David J. Brull,&nbsp;Peter Gohlke,&nbsp;John R. Payne,&nbsp;Michael World,&nbsp;Birger Thorsteinsson,&nbsp;Steve E. Humphries,&nbsp;Hugh E. Montgomery","doi":"10.1002/icl3.1019","DOIUrl":"10.1002/icl3.1019","url":null,"abstract":"<div>\u0000 <p>Uncoupling proteins (UCPs) regulate mitochondrial function, and thus cellular metabolism. Angiotensin-converting enzyme (ACE) is the central component of endocrine and local tissue renin–angiotensin systems (RAS), which also regulate diverse aspects of whole-body metabolism and mitochondrial function (partly through altering mitochondrial UCP expression). We show that ACE expression also appears to be <i>regulated by</i> mitochondrial UCPs. In genetic analysis of two unrelated populations (<i>healthy young UK men</i> and <i>Scandinavian diabetic patients</i>) serum ACE (sACE) activity was significantly higher amongst <i>UCP3-55C</i> (rather than T) and <i>UCP2</i> I (rather than D) allele carriers. RNA interference against UCP2 in human umbilical vein endothelial cells reduced UCP2 mRNA sixfold (<i>P</i> &lt; 0·01) whilst increasing ACE expression within a physiological range (&lt;1·8-fold at 48 h; <i>P</i> &lt; 0·01). Our findings suggest novel hypotheses. Firstly, cellular feedback regulation may occur between UCPs and ACE. Secondly, <i>cellular</i> UCP regulation of <i>sACE</i> suggests a novel means of crosstalk between (and mutual regulation of) cellular and endocrine metabolism. This might partly explain the reduced risk of developing diabetes and metabolic syndrome with RAS antagonists and offer insight into the origins of cardiovascular disease in which UCPs and ACE both play a role.</p>\u0000 </div>","PeriodicalId":91499,"journal":{"name":"Inside the cell","volume":"1 1","pages":"70-81"},"PeriodicalIF":0.0,"publicationDate":"2015-08-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1002/icl3.1019","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"34679155","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}

{"title":"Transmissible cancers in an evolutionary context","authors":"Beata Ujvari,&nbsp;Anthony T. Papenfuss,&nbsp;Katherine Belov","doi":"10.1002/icl3.1020","DOIUrl":"https://doi.org/10.1002/icl3.1020","url":null,"abstract":"<div>\u0000 <p>Cancer is an evolutionary and ecological process in which complex interactions between tumour cells and their environment share many similarities with organismal evolution. Tumour cells with highest adaptive potential have a selective advantage over less fit cells. Naturally occurring transmissible cancers provide an ideal model system for investigating the evolutionary arms race between cancer cells and their surrounding micro-environment and macro-environment. However, the evolutionary landscapes in which contagious cancers reside have not been subjected to comprehensive investigation. Here, we provide a multifocal analysis of transmissible tumour progression and discuss the selection forces that shape it. We demonstrate that transmissible cancers adapt to both their micro-environment and macro-environment, and evolutionary theories applied to organisms are also relevant to these unique diseases. The three naturally occurring transmissible cancers, canine transmissible venereal tumour (CTVT) and Tasmanian devil facial tumour disease (DFTD) and the recently discovered clam leukaemia, exhibit different evolutionary phases: (i) CTVT, the oldest naturally occurring cell line is remarkably stable; (ii) DFTD exhibits the signs of stepwise cancer evolution; and (iii) clam leukaemia shows genetic instability. While all three contagious cancers carry the signature of ongoing and fairly recent adaptations to selective forces, CTVT appears to have reached an evolutionary stalemate with its host, while DFTD and the clam leukaemia appear to be still at a more dynamic phase of their evolution. Parallel investigation of contagious cancer genomes and transcriptomes and of their micro-environment and macro-environment could shed light on the selective forces shaping tumour development at different time points: during the progressive phase and at the endpoint. A greater understanding of transmissible cancers from an evolutionary ecology perspective will provide novel avenues for the prevention and treatment of both contagious and non-communicable cancers.</p>\u0000 </div>","PeriodicalId":91499,"journal":{"name":"Inside the cell","volume":"1 1","pages":"17-26"},"PeriodicalIF":0.0,"publicationDate":"2015-07-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1002/icl3.1020","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"137653673","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}