Abstract:
:Scaffolding proteins play pivotal roles in the assembly of macromolecular machines such as the spliceosome. The adaptor protein CD2BP2, originally identified as a binding partner of the adhesion molecule CD2, is a pre-spliceosomal assembly factor that utilizes its glycine-tyrosine-phenylalanine (GYF) domain to co-localize with spliceosomal proteins. So far, its function in vertebrates is unknown. Using conditional gene targeting in mice, we show that CD2BP2 is crucial for embryogenesis, leading to growth retardation, defects in vascularization, and premature death at embryonic day 10.5 when absent. Ablation of the protein in bone marrow-derived macrophages indicates that CD2BP2 is involved in the alternative splicing of mRNA transcripts from diverse origins. At the molecular level, we identified the phosphatase PP1 to be recruited to the spliceosome via the N-terminus of CD2BP2. Given the strong expression of CD2BP2 in podocytes of the kidney, we use selective depletion of CD2BP2, in combination with next-generation sequencing, to monitor changes in exon usage of genes critical for podocyte functions, including VEGF and actin regulators. CD2BP2-depleted podocytes display foot process effacement, and cause proteinuria and ultimately lethal kidney failure in mice. Collectively, our study defines CD2BP2 as a non-redundant splicing factor essential for embryonic development and podocyte integrity.
journal_name
J Mol Cell Bioljournal_title
Journal of molecular cell biologyauthors
Albert GI,Schell C,Kirschner KM,Schäfer S,Naumann R,Müller A,Kretz O,Kuropka B,Girbig M,Hübner N,Krause E,Scholz H,Huber TB,Knobeloch KP,Freund Cdoi
10.1093/jmcb/mjv039subject
Has Abstractpub_date
2015-10-01 00:00:00pages
402-14issue
5eissn
1674-2788issn
1759-4685pii
mjv039journal_volume
7pub_type
杂志文章abstract::Glioblastoma multiforme (GBM) is a highly invasive brain tumor with limited therapeutic means and poor prognosis. Recent studies indicate that glioma-initiating cells/glioma stem cells (GICs/GSCs) may be responsible for tumor initiation, infiltration, and recurrence. GICs could aberrantly employ molecular machinery ba...
journal_title:Journal of molecular cell biology
pub_type: 杂志文章
doi:10.1093/jmcb/mjx017
更新日期:2017-08-01 00:00:00
abstract::The mammalian target of rapamycin (mTOR) is a protein kinase that plays key roles in cellular regulation. It forms complexes with additional proteins. The best-understood one is mTOR complex 1 (mTORC1). The regulation and cellular functions of mTORC1 have been the subjects of intense study; despite this, many question...
journal_title:Journal of molecular cell biology
pub_type: 杂志文章,评审
doi:10.1093/jmcb/mjq038
更新日期:2011-08-01 00:00:00
abstract::MEK inhibitor has been highlighted as a promising anti-tumor drug but its effect has been reported as varying over a wide range depending on patho-physiological conditions. In this study, we employed a systems approach by combining biochemical experimentation with in silico simulations to investigate the resistance me...
journal_title:Journal of molecular cell biology
pub_type: 杂志文章
doi:10.1093/jmcb/mjs021
更新日期:2012-06-01 00:00:00
abstract::The Hippo signalling pathway has a crucial role in growth control during development, and its dysregulation contributes to tumorigenesis. Recent studies uncover multiple upstream regulatory inputs into Hippo signalling, which affects phosphorylation of the transcriptional coactivator Yki/YAP/TAZ by Wts/Lats. Here we i...
journal_title:Journal of molecular cell biology
pub_type: 杂志文章
doi:10.1093/jmcb/mjw036
更新日期:2016-08-01 00:00:00
abstract::OspE, a Shigella type III effector binds to integrin-like kinase and enhances cell adhesion to better disseminate and colonize the intestinal epithelium. Because of the existence of OspE orthologues in other enteropathogens such as enteropathogenic Escherichia coli or Salmonella sp., maintenance of cell adhesion appea...
journal_title:Journal of molecular cell biology
pub_type: 杂志文章
doi:10.1093/jmcb/mjp013
更新日期:2009-12-01 00:00:00
abstract::Ever since gene targeting or specific modification of genome sequences in mice was achieved in the early 1980s, the reverse genetic approach of precise editing of any genomic locus has greatly accelerated biomedical research and biotechnology development. In particular, the recent development of the CRISPR/Cas9 system...
journal_title:Journal of molecular cell biology
pub_type: 杂志文章
doi:10.1093/jmcb/mjaa060
更新日期:2020-10-30 00:00:00
abstract::Type 2 immune response has been shown to facilitate cold-induced thermogenesis and browning of white fat. However, whether alternatively activated macrophages produce catecholamine and substantially promote adaptive thermogenesis in adipose tissue remains controversial. Here, we show that tyrosine hydroxylase (TyrH), ...
journal_title:Journal of molecular cell biology
pub_type: 杂志文章
doi:10.1093/jmcb/mjx046
更新日期:2017-10-01 00:00:00
abstract::As many human sensory and cognitive diseases are caused by irreversible damage or loss of certain types of neurons, methodologies aimed at replacement of lost neurons are key to restore lost sensation. Recent advances in generation of ear-cell progenitors, optic-cup structures and cortical neurons from human embryonic...
journal_title:Journal of molecular cell biology
pub_type: 杂志文章,评审
doi:10.1093/jmcb/mjs060
更新日期:2013-04-01 00:00:00
abstract::Mammalian fertilization involves membrane events-adhesion, fusion, sperm engulfment, membrane block to polyspermy-whose causes remain largely unknown. Recently, specific oscillations of the sperm in contact with the egg were shown to be necessary for fusion. Using a microfluidic chip to impose the venue for the encoun...
journal_title:Journal of molecular cell biology
pub_type: 杂志文章
doi:10.1093/jmcb/mjy005
更新日期:2018-12-01 00:00:00
abstract::Advances in functional genomics have led to discovery of a large group of previous uncharacterized long non-coding RNAs (lncRNAs). Emerging evidence indicates that lncRNAs may serve as master gene regulators through various mechanisms. Dysregulation of lncRNAs is often associated with a variety of human diseases inclu...
journal_title:Journal of molecular cell biology
pub_type: 杂志文章,评审
doi:10.1093/jmcb/mju013
更新日期:2014-06-01 00:00:00
abstract::Our earlier studies have demonstrated that the cigarette smoke in the form of cigarette smoke condensate (CSC) causes growth arrest of a mouse spermatocyte cell line [GC-2spd(ts)] through activation of the AHR-NRF2 pathway. The present study demonstrates the CSC-activated p38 and ERK MAPK signaling in GC-2spd(ts) via ...
journal_title:Journal of molecular cell biology
pub_type: 杂志文章
doi:10.1093/jmcb/mju049
更新日期:2015-02-01 00:00:00
abstract::T-cell intracellular antigen (TIA)-1 and TIA-1-related protein (TIAR) are mRNA-binding proteins that can aggregate within granules under specific stress conditions. In this study, we analyzed TIAR/TIA-1 aggregation under different hypoxic conditions, and studied the effects on the hypoxia-inducible factor (HIF)-1α in ...
journal_title:Journal of molecular cell biology
pub_type: 杂志文章
doi:10.1093/jmcb/mjq032
更新日期:2010-12-01 00:00:00
abstract::Human colon carcinomas (CCs) represent a growing worldwide problem. One of the pathways that has been negatively implicated in the genesis of CCs is triggered by bone morphogenetic protein (BMP) ligands, which activate BMP receptors leading to the function of SMAD proteins in the nucleus. BMP signaling is altered in f...
journal_title:Journal of molecular cell biology
pub_type: 杂志文章
doi:10.1093/jmcb/mjq035
更新日期:2010-12-01 00:00:00
abstract::The SMYD (SET and MYND domain) family of lysine methyltransferases (KMTs) plays pivotal roles in various cellular processes, including gene expression regulation and DNA damage response. Initially identified as genuine histone methyltransferases, specific members of this family have recently been shown to methylate no...
journal_title:Journal of molecular cell biology
pub_type: 杂志文章
doi:10.1093/jmcb/mjr025
更新日期:2011-10-01 00:00:00
abstract::Haploid pluripotent stem cells, such as haploid embryonic stem cells (haESCs), facilitate the genetic study of recessive traits. In vitro, fish haESCs maintain haploidy in both undifferentiated and differentiated states, but whether mammalian haESCs can preserve pluripotency in the haploid state has not been tested. H...
journal_title:Journal of molecular cell biology
pub_type: 杂志文章
doi:10.1093/jmcb/mjv044
更新日期:2015-08-01 00:00:00
abstract::We previously identified that hepatitis B virus (HBV) encodes a microRNA (HBV-miR-3) that restrains HBV replication by targeting the HBV transcript. However, whether HBV-miR-3 affects host innate immunity to modulate HBV replication remains unclear. Here, we examined the vital functions of HBV-miR-3 in the innate immu...
journal_title:Journal of molecular cell biology
pub_type: 杂志文章
doi:10.1093/jmcb/mjz104
更新日期:2020-05-18 00:00:00
abstract::SRY-related HMG-box gene 2 (SOX2) is one of the key regulatory genes that maintain the pluripotency and self-renewal properties in embryonic stem cells. Here we used immunohistochemistry to analyze the expression of SOX2 in human prostate tissues and found it contributed to tumorigenesis and correlated with histologic...
journal_title:Journal of molecular cell biology
pub_type: 杂志文章
doi:10.1093/jmcb/mjr002
更新日期:2011-08-01 00:00:00
abstract::The ectoderm has the capability to generate epidermis and neuroectoderm and plays imperative roles during the early embryonic development. Our recent study uncovered a region with ectodermal progenitor potential in mouse embryo at embryonic day 7.0 and revealed that Nodal inhibition is essential for its formation. Her...
journal_title:Journal of molecular cell biology
pub_type: 杂志文章
doi:10.1093/jmcb/mjv030
更新日期:2015-10-01 00:00:00
abstract::Understanding the mechanism of how cholangiocytes (liver ductal cells) are activated upon liver injury and specified to hepatocytes would permit liver regenerative medicine. Here we achieved long-term in vitro expansion of mouse liver organoids by modulating signaling pathways with a combination of three small-molecul...
journal_title:Journal of molecular cell biology
pub_type: 杂志文章
doi:10.1093/jmcb/mjaa010
更新日期:2020-08-01 00:00:00
abstract::We present a computational study of tissue transcriptomic data of 14 cancer types to address: what may drive cancer cell division? Our analyses point to that persistent disruption of the intracellular pH by Fenton reactions may be at the root of cancer development. Specifically, we have statistically demonstrated that...
journal_title:Journal of molecular cell biology
pub_type: 杂志文章
doi:10.1093/jmcb/mjy039
更新日期:2018-10-01 00:00:00
abstract::The cranial neural crest (CNC) cells play a vital role in craniofacial development and regeneration. They are multi-potent progenitors, being able to differentiate into various types of tissues. Both pre-migratory and post-migratory CNC cells are plastic, taking on diverse fates by responding to different inductive si...
journal_title:Journal of molecular cell biology
pub_type: 杂志文章
doi:10.1093/jmcb/mjv052
更新日期:2015-10-01 00:00:00
abstract::Hematopoietic stem cells (HSCs) replenish all types of blood cells. It is debating whether HSCs in adults solely originate from the aorta-gonad-mesonephros (AGM) region, more specifically, the dorsal aorta, during embryogenesis. Here, we report that somite hematopoiesis, a previously unwitnessed hematopoiesis, can gen...
journal_title:Journal of molecular cell biology
pub_type: 杂志文章
doi:10.1093/jmcb/mjw024
更新日期:2016-08-01 00:00:00
abstract::Embryonic stem cells (ESCs) exhibit unique chromatin features, including a permissive transcriptional program and an open, decondensed chromatin state. Induced pluripotent stem cells (iPSCs), which are very similar to ESCs, hold great promise for therapy and basic research. However, the mechanisms by which reprogrammi...
journal_title:Journal of molecular cell biology
pub_type: 杂志文章
doi:10.1093/jmcb/mjr028
更新日期:2011-12-01 00:00:00
abstract::Histone deacetylase 1 (HDAC1) is an essential epigenetic regulator belonging to a highly conserved family of deacetylases. Increased HDAC1 activity and expression often correlates with neoplastic transformation. Here we show how specific modification of HDAC1 by SUMO1, but not by SUMO2, facilitates HDAC1 degradation. ...
journal_title:Journal of molecular cell biology
pub_type: 杂志文章
doi:10.1093/jmcb/mjt032
更新日期:2013-12-01 00:00:00
abstract::Analysis linking directly genomics, neuroimaging phenotypes and clinical measurements is crucial for understanding psychiatric disorders, but remains rare. Here, we describe a multi-scale analysis using genome-wide SNPs, gene expression, grey matter volume (GMV), and the positive and negative syndrome scale scores (PA...
journal_title:Journal of molecular cell biology
pub_type: 杂志文章
doi:10.1093/jmcb/mjy071
更新日期:2019-08-19 00:00:00
abstract::Cells encountering hypoxic stress conserve resources and energy by downregulating the protein synthesis. Here we demonstrate that one mechanism in this response is the translational repression of TOP mRNAs that encode components of the translational apparatus. This mode of regulation involves TSC and Rheb, as knockout...
journal_title:Journal of molecular cell biology
pub_type: 杂志文章
doi:10.1093/jmcb/mju008
更新日期:2014-06-01 00:00:00
abstract::Local signaling events at synapses or axon terminals are communicated to the nucleus to elicit transcriptional responses, and thereby translate information about the external environment into internal neuronal representations. This retrograde signaling is critical to dendritic growth, synapse development, and neuronal...
journal_title:Journal of molecular cell biology
pub_type: 杂志文章
doi:10.1093/jmcb/mjaa058
更新日期:2020-10-26 00:00:00
abstract::The involvement of microRNAs (miRNAs) in the development of the neural crest (NC) cells and other neuronal differentiation is still poorly understood. Here, we investigated the global function of miRNAs in embryonic development by examining the Wnt1-cre-mediated Dicer knockout mice. Dicer ablation resulted in malforma...
journal_title:Journal of molecular cell biology
pub_type: 杂志文章
doi:10.1093/jmcb/mjq008
更新日期:2010-06-01 00:00:00
abstract::Bacteria and archaea encode members of the large multiple antibiotic resistance regulator (MarR) family of transcriptional regulators. Generally, MarR homologs regulate activity of genes involved in antibiotic resistance, stress responses, virulence or catabolism of aromatic compounds. They constitute a diverse group ...
journal_title:Journal of molecular cell biology
pub_type: 杂志文章
doi:10.1093/jmcb/mjq021
更新日期:2010-10-01 00:00:00
abstract::E-selectin is a cell-adhesion molecule of the vascular endothelium that promotes essential leukocyte rolling in the early inflammatory response by binding to glycoproteins containing the tetrasaccharide sialyl Lewis(x) (sLe(x)). Efficient leukocyte recruitment under vascular flow conditions depends on an increased lif...
journal_title:Journal of molecular cell biology
pub_type: 杂志文章
doi:10.1093/jmcb/mjv046
更新日期:2016-02-01 00:00:00