BMC Cell Biology最新文献

{"title":"Expression and function of pannexins in the inner ear and hearing.","authors":"Hong-Bo Zhao","doi":"10.1186/s12860-016-0095-7","DOIUrl":"https://doi.org/10.1186/s12860-016-0095-7","url":null,"abstract":"<p><p>Pannexin (Panx) is a gene family encoding gap junction proteins in vertebrates. So far, three isoforms (Panx1, 2 and 3) have been identified. All of three Panx isoforms express in the cochlea with distinct expression patterns. Panx1 expresses in the cochlea extensively, including the spiral limbus, the organ of Corti, and the cochlear lateral wall, whereas Panx2 and Panx3 restrict to the basal cells of the stria vascularis in the lateral wall and the cochlear bony structure, respectively. However, there is no pannexin expression in auditory sensory hair cells. Recent studies demonstrated that like connexin gap junction gene, Panx1 deficiency causes hearing loss. Panx1 channels dominate ATP release in the cochlea. Deletion of Panx1 abolishes ATP release in the cochlea and reduces endocochlear potential (EP), auditory receptor current/potential, and active cochlear amplification. Panx1 deficiency in the cochlea also activates caspase-3 cell apoptotic pathway leading to cell degeneration. These new findings suggest that pannexins have a critical role in the cochlea in regard to hearing. However, detailed information about pannexin function in the cochlea and Panx mutation induced hearing loss still remain largely undetermined. Further studies are required. </p>","PeriodicalId":9051,"journal":{"name":"BMC Cell Biology","volume":"17 Suppl 1 ","pages":"16"},"PeriodicalIF":0.0,"publicationDate":"2016-05-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1186/s12860-016-0095-7","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"34521969","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":"Molecular mechanisms regulating formation, trafficking and processing of annular gap junctions.","authors":"Matthias M Falk,&nbsp;Cheryl L Bell,&nbsp;Rachael M Kells Andrews,&nbsp;Sandra A Murray","doi":"10.1186/s12860-016-0087-7","DOIUrl":"https://doi.org/10.1186/s12860-016-0087-7","url":null,"abstract":"<p><p>Internalization of gap junction plaques results in the formation of annular gap junction vesicles. The factors that regulate the coordinated internalization of the gap junction plaques to form annular gap junction vesicles, and the subsequent events involved in annular gap junction processing have only relatively recently been investigated in detail. However it is becoming clear that while annular gap junction vesicles have been demonstrated to be degraded by autophagosomal and endo-lysosomal pathways, they undergo a number of additional processing events. Here, we characterize the morphology of the annular gap junction vesicle and review the current knowledge of the processes involved in their formation, fission, fusion, and degradation. In addition, we address the possibility for connexin protein recycling back to the plasma membrane to contribute to gap junction formation and intercellular communication. Information on gap junction plaque removal from the plasma membrane and the subsequent processing of annular gap junction vesicles is critical to our understanding of cell-cell communication as it relates to events regulating development, cell homeostasis, unstable proliferation of cancer cells, wound healing, changes in the ischemic heart, and many other physiological and pathological cellular phenomena. </p>","PeriodicalId":9051,"journal":{"name":"BMC Cell Biology","volume":"17 Suppl 1 ","pages":"22"},"PeriodicalIF":0.0,"publicationDate":"2016-05-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1186/s12860-016-0087-7","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"34523007","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":"Role of connexins and pannexins during ontogeny, regeneration, and pathologies of bone.","authors":"Lilian I Plotkin,&nbsp;Dale W Laird,&nbsp;Joelle Amedee","doi":"10.1186/s12860-016-0088-6","DOIUrl":"https://doi.org/10.1186/s12860-016-0088-6","url":null,"abstract":"<p><p>Electron micrographs revealed the presence of gap junctions in osteoblastic cells over 40 years ago. These intercellular channels formed from connexins are present in bone forming osteoblasts, bone resorbing osteoclasts, and osteocytes (mature osteoblasts embedded in the mineralized bone matrix). More recently, genetic and pharmacologic studies revealed the role of connexins, and in particular Cx43, in the differentiation and function of all bone types. Furthermore, mutations in the gene encoding Cx43 were found to be causally linked to oculodentodigital dysplasia, a condition that results in an abnormal skeleton. Pannexins, molecules with similar structure and single-membrane channel forming potential as connexins when organized as hemichannels, are also expressed in osteoblastic cells. The function of pannexins in bone and cartilage is beginning to be uncovered, but more research is needed to determine the role of pannexins in bone development, adult bone mass and skeletal homeostasis. We describe here the current knowledge on the role of connexins and pannexins on skeletal health and disease. </p>","PeriodicalId":9051,"journal":{"name":"BMC Cell Biology","volume":"17 Suppl 1 ","pages":"19"},"PeriodicalIF":0.0,"publicationDate":"2016-05-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1186/s12860-016-0088-6","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"34522207","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":"Regulation of gap junction channels and hemichannels by phosphorylation and redox changes: a revision.","authors":"Kristin Pogoda,&nbsp;Petra Kameritsch,&nbsp;Mauricio A Retamal,&nbsp;José L Vega","doi":"10.1186/s12860-016-0099-3","DOIUrl":"https://doi.org/10.1186/s12860-016-0099-3","url":null,"abstract":"<p><p>Post-translational modifications of connexins play an important role in the regulation of gap junction and hemichannel permeability. The prerequisite for the formation of functional gap junction channels is the assembly of connexin proteins into hemichannels and their insertion into the membrane. Hemichannels can affect cellular processes by enabling the passage of signaling molecules between the intracellular and extracellular space. For the intercellular communication hemichannels from one cell have to dock to its counterparts on the opposing membrane of an adjacent cell to allow the transmission of signals via gap junctions from one cell to the other. The controlled opening of hemichannels and gating properties of complete gap junctions can be regulated via post-translational modifications of connexins. Not only channel gating, but also connexin trafficking and assembly into hemichannels can be affected by post-translational changes. Recent investigations have shown that connexins can be modified by phosphorylation/dephosphorylation, redox-related changes including effects of nitric oxide (NO), hydrogen sulfide (H2S) or carbon monoxide (CO), acetylation, methylation or ubiquitination. Most of the connexin isoforms are known to be phosphorylated, e.g. Cx43, one of the most studied connexin at all, has 21 reported phosphorylation sites. In this review, we provide an overview about the current knowledge and relevant research of responsible kinases, connexin phosphorylation sites and reported effects on gap junction and hemichannel regulation. Regarding the effects of oxidants we discuss the role of NO in different cell types and tissues and recent studies about modifications of connexins by CO and H2S. </p>","PeriodicalId":9051,"journal":{"name":"BMC Cell Biology","volume":"17 Suppl 1 ","pages":"11"},"PeriodicalIF":0.0,"publicationDate":"2016-05-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1186/s12860-016-0099-3","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"34585660","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":"Connexins and pannexins in neuronal development and adult neurogenesis.","authors":"Leigh Anne Swayne, Steffany A L Bennett","doi":"10.1186/s12860-016-0089-5","DOIUrl":"10.1186/s12860-016-0089-5","url":null,"abstract":"<p><p>Connexins and pannexins share very similar structures and functions; they also exhibit overlapping expression in many stages of neuronal development. Here, we review evidence implicating connexin- and pannexin-mediated communication in the regulation of the birth and development of neurons, specifically Cx26, Cx30, Cx32, Cx36, Cx43, Cx45, Panx1, and Panx2. We begin by dissecting the involvement of these proteins in the generation and development of new neurons in the embryonic, postnatal, and adult brain. Next we briefly outline common mechanisms employed by both pannexins and connexins in these roles, including modulation of purinergic receptor signalling and signalling nexus functions. Throughout this review we highlight developing themes as well as important gaps in knowledge to be bridged. </p>","PeriodicalId":9051,"journal":{"name":"BMC Cell Biology","volume":"17 Suppl 1 ","pages":"10"},"PeriodicalIF":0.0,"publicationDate":"2016-05-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1186/s12860-016-0089-5","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"34587458","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":"Activity-dependent plasticity of electrical synapses: increasing evidence for its presence and functional roles in the mammalian brain.","authors":"Julie S Haas,&nbsp;Corey M Greenwald,&nbsp;Alberto E Pereda","doi":"10.1186/s12860-016-0090-z","DOIUrl":"https://doi.org/10.1186/s12860-016-0090-z","url":null,"abstract":"<p><p>Gap junctions mediate electrical synaptic transmission between neurons. While the actions of neurotransmitter modulators on the conductance of gap junctions have been extensively documented, increasing evidence indicates they can also be influenced by the ongoing activity of neural networks, in most cases via local interactions with nearby glutamatergic synapses. We review here early evidence for the existence of activity-dependent regulatory mechanisms as well recent examples reported in mammalian brain. The ubiquitous distribution of both neuronal connexins and the molecules involved suggest this phenomenon is widespread and represents a property of electrical transmission in general. </p>","PeriodicalId":9051,"journal":{"name":"BMC Cell Biology","volume":"17 Suppl 1 ","pages":"14"},"PeriodicalIF":0.0,"publicationDate":"2016-05-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1186/s12860-016-0090-z","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"34418280","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":"The absence of dysferlin induces the expression of functional connexin-based hemichannels in human myotubes.","authors":"Luis A Cea,&nbsp;Jorge A Bevilacqua,&nbsp;Christian Arriagada,&nbsp;Ana María Cárdenas,&nbsp;Anne Bigot,&nbsp;Vincent Mouly,&nbsp;Juan C Sáez,&nbsp;Pablo Caviedes","doi":"10.1186/s12860-016-0096-6","DOIUrl":"https://doi.org/10.1186/s12860-016-0096-6","url":null,"abstract":"<p><strong>Background: </strong>Mutations in the gene encoding for dysferlin cause recessive autosomal muscular dystrophies called dysferlinopathies. These mutations induce several alterations in skeletal muscles, including, inflammation, increased membrane permeability and cell death. Despite the fact that the etiology of dysferlinopathies is known, the mechanism that explains the aforementioned alterations is still elusive. Therefore, we have now evaluated the potential involvement of connexin based hemichannels in the pathophysiology of dysferlinopathies.</p><p><strong>Results: </strong>Human deltoid muscle biopsies of 5 Chilean dysferlinopathy patients exhibited the presence of muscular connexins (Cx40.1, Cx43 and Cx45). The presence of these connexins was also observed in human myotubes derived from immortalized myoblasts derived from other patients with mutated forms of dysferlin. In addition to the aforementioned connexins, these myotubes expressed functional connexin based hemichannels, evaluated by ethidium uptake assays, as opposed to myotubes obtained from a normal human muscle cell line, RCMH. This response was reproduced in a knock-down model of dysferlin, by treating RCMH cell line with small hairpin RNA specific for dysferlin (RCMH-sh Dysferlin). Also, the presence of P2X7 receptor and the transient receptor potential channel, TRPV2, another Ca(2+) permeable channels, was detected in the myotubes expressing mutated dysferlin, and an elevated resting intracellular Ca(2+) level was found in the latter myotubes, which was in turn reduced to control levels in the presence of the molecule D4, a selective Cx HCs inhibitor.</p><p><strong>Conclusions: </strong>The data suggests that dysferlin deficiency, caused by mutation or downregulation of dysferlin, promotes the expression of Cx HCs. Then, the de novo expression Cx HC causes a dysregulation of intracellular free Ca(2+) levels, which could underlie muscular damage associated to dysferlin mutations. This mechanism could constitute a potential therapeutical target in dysferlinopathies.</p>","PeriodicalId":9051,"journal":{"name":"BMC Cell Biology","volume":"17 Suppl 1 ","pages":"15"},"PeriodicalIF":0.0,"publicationDate":"2016-05-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1186/s12860-016-0096-6","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"34522478","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":"Connexinopathies: a structural and functional glimpse.","authors":"Isaac E García, Pavel Prado, Amaury Pupo, Oscar Jara, Diana Rojas-Gómez, Paula Mujica, Carolina Flores-Muñoz, Jorge González-Casanova, Carolina Soto-Riveros, Bernardo I Pinto, Mauricio A Retamal, Carlos González, Agustín D Martínez","doi":"10.1186/s12860-016-0092-x","DOIUrl":"10.1186/s12860-016-0092-x","url":null,"abstract":"<p><p>Mutations in human connexin (Cx) genes have been related to diseases, which we termed connexinopathies. Such hereditary disorders include nonsyndromic or syndromic deafness (Cx26, Cx30), Charcot Marie Tooth disease (Cx32), occulodentodigital dysplasia and cardiopathies (Cx43), and cataracts (Cx46, Cx50). Despite the clinical phenotypes of connexinopathies have been well documented, their pathogenic molecular determinants remain elusive. The purpose of this work is to identify common/uncommon patterns in channels function among Cx mutations linked to human diseases. To this end, we compiled and discussed the effect of mutations associated to Cx26, Cx32, Cx43, and Cx50 over gap junction channels and hemichannels, highlighting the function of the structural channel domains in which mutations are located and their possible role affecting oligomerization, gating and perm/selectivity processes. </p>","PeriodicalId":9051,"journal":{"name":"BMC Cell Biology","volume":"17 Suppl 1 ","pages":"17"},"PeriodicalIF":0.0,"publicationDate":"2016-05-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4896260/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"34428728","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":"Proceedings of the International Gap Junction Conference 2015.","authors":"Juan C Sáez","doi":"10.1186/s12860-016-0097-5","DOIUrl":"https://doi.org/10.1186/s12860-016-0097-5","url":null,"abstract":"","PeriodicalId":9051,"journal":{"name":"BMC Cell Biology","volume":"17 Suppl 1 ","pages":"18"},"PeriodicalIF":0.0,"publicationDate":"2016-05-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1186/s12860-016-0097-5","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"34522719","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":"Matrix metalloproteinase 9 induces endothelial-mesenchymal transition via Notch activation in human kidney glomerular endothelial cells.","authors":"Ye Zhao,&nbsp;Xi Qiao,&nbsp;Lihua Wang,&nbsp;Tian Kui Tan,&nbsp;Hong Zhao,&nbsp;Yun Zhang,&nbsp;Jianlin Zhang,&nbsp;Padmashree Rao,&nbsp;Qi Cao,&nbsp;Yiping Wang,&nbsp;Ya Wang,&nbsp;Yuan Min Wang,&nbsp;Vincent W S Lee,&nbsp;Stephen I Alexander,&nbsp;David C H Harris,&nbsp;Guoping Zheng","doi":"10.1186/s12860-016-0101-0","DOIUrl":"https://doi.org/10.1186/s12860-016-0101-0","url":null,"abstract":"<p><strong>Background: </strong>Endothelial-mesenchymal transition (EndoMT) is a major source of myofibroblast formation in kidney fibrosis. Our previous study showed a profibrotic role for matrix metalloproteinase 9 (MMP-9) in kidney fibrosis via induction of epithelial-mesenchymal transition (EMT). Inhibition of MMP-9 activity reduced kidney fibrosis in murine unilateral ureteral obstruction. This study investigated whether MMP-9 also plays a role in EndoMT in human glomerular endothelial cells.</p><p><strong>Results: </strong>TGF-β1 (10 or 20 ng/ml) induced EndoMT in HKGECs as shown by morphological changes. In addition, VE-cadherin and CD31 were significantly downregulated, whereas α-SMA, vimentin, and N-cadherin were upregulated. RT-PCR revealed that Snail, a known inducer of EMT, was upregulated. The MMP inhibitor GM6001 abrogated TGF-β1-induced EndoMT. Zymography indicated that MMP-9 was also upregulated in TGF-β1-treated HKGECs. Recombinant MMP-9 (2 μg/ml) induced EndoMT in HKGECs via Notch signaling, as evidenced by increased formation of the Notch intracellular domain (NICD) and decreased Notch 1. Inhibition of MMP-9 activity by its inhibitor showed a dose-dependent response in preventing TGF-β1-induced α-SMA and NICD in HKGECs, whereas inhibition of Notch signaling by γ-secretase inhibitor (GSI) blocked rMMP-9-induced EndoMT.</p><p><strong>Conclusions: </strong>Taken together, our results demonstrate that MMP-9 plays an important role in TGF-β1-induced EndoMT via upregulation of Notch signaling in HKGECs.</p>","PeriodicalId":9051,"journal":{"name":"BMC Cell Biology","volume":"17 1","pages":"21"},"PeriodicalIF":0.0,"publicationDate":"2016-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1186/s12860-016-0101-0","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"34346520","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}