Abstract：
:Protein isoforms generated by alternative splicing contribute to proteome diversity. Because of the lack of effective techniques, the isoform-specific function, expression, localization, and signaling of endogenous proteins are unknown for most genes. Here, we report a genetic method, isoTarget, for multi-purpose studies of targeted isoforms in select cells. Applying isoTarget to two isoforms of Drosophila Dscam, Dscam[TM1] and [TM2], we found that, in neurons, endogenous Dscam[TM1] is in dendrites, whereas Dscam[TM2] is in both dendrites and axons. We demonstrate that the difference in subcellular localization, rather than biochemical properties, leads to the two isoforms' functional differences. Moreover, we show that the subcellular enrichment of functional partners results in a DLK/Wallenda-Dscam[TM2]-Dock signaling cascade in axons. We further apply isoTarget to study two isoforms of a GABA receptor to demonstrate its general applicability. isoTarget is an effective technique for studying how alternative splicing enhances proteome complexity.
journal_name
Cell Repjournal_title
Cell reportsauthors
Liu H,Pizzano S,Li R,Zhao W,Veling MW,Hu Y,Yang L,Ye Bdoi
10.1016/j.celrep.2020.108361subject
Has Abstractpub_date
2020-11-10 00:00:00pages
108361issue
6issn
2211-1247pii
S2211-1247(20)31350-4journal_volume
33pub_type
杂志文章相关文献
Cell Reports文献大全abstract：:In metazoans, the nuclear envelope (NE) breakdown (NEBD) occurs during "open" mitosis and meiosis. In the fission yeast Schizosaccharomyces pombe, the mitosis and the first meiotic division (MI) are "closed," during which the NE is maintained. Intriguingly, during the second meiotic division (MII), the NE is also main...
journal_title：Cell reports
pub_type： 杂志文章
doi：10.1016/j.celrep.2018.03.073
更新日期：2018-04-24 00:00:00
abstract：:The H3K4me3 demethylase Kdm5a regulates gene transcription and is implicated in carcinogenesis. However, the role of Kdm5a in innate immune response remains poorly understood. Here, we demonstrate that Kdm5a deficiency impairs activation of natural killer (NK) cells, with decreased IFN-γ production. Accordingly, Kdm5a...
journal_title：Cell reports
pub_type： 杂志文章
doi：10.1016/j.celrep.2016.03.035
更新日期：2016-04-12 00:00:00
abstract：:The CARMA1/CARD11-BCL10-MALT1 (CBM) complex bridges T and B cell antigen receptor (TCR/BCR) ligation to MALT1 protease activation and canonical nuclear factor κB (NF-κB) signaling. Using unbiased mass spectrometry, we discover multiple serine phosphorylation sites in the MALT1 C terminus after T cell activation. Phosp...
journal_title：Cell reports
pub_type： 杂志文章
doi：10.1016/j.celrep.2019.09.040
更新日期：2019-10-22 00:00:00
abstract：:Chimeric antigen receptor (CAR) T cell therapy has proven clinically beneficial against B cell acute lymphoblastic leukemia and non-Hodgkin's lymphoma. However, suboptimal clinical outcomes have been associated with decreased expansion and persistence of adoptively transferred CAR T cells, antigen-negative relapses, a...
journal_title：Cell reports
pub_type： 杂志文章
doi：10.1016/j.celrep.2018.04.051
更新日期：2018-05-15 00:00:00
abstract：:Medium spiny neurons (MSNs) of mice show opposing activities upon the initiation of a food-seeking lever press task. Ventromedial striatal (VMS)-MSNs are inhibited but ventrolateral striatal (VLS)-MSNs are activated; these activities mediate action selection and action initiation, respectively. To understand what inpu...
journal_title：Cell reports
pub_type： 杂志文章
doi：10.1016/j.celrep.2020.107829
更新日期：2020-06-30 00:00:00
abstract：:ASXL2 is an ETP family protein that interacts with PPARγ. We find that ASXL2-/- mice are insulin resistant, lipodystrophic, and fail to respond to a high-fat diet. Consistent with genetic variation at the ASXL2 locus and human bone mineral density, ASXL2-/- mice are also severely osteopetrotic because of failed osteoc...
journal_title：Cell reports
pub_type： 杂志文章
doi：10.1016/j.celrep.2015.05.019
更新日期：2015-06-16 00:00:00
abstract：:The heavy chain IGHV1-69 germline gene exhibits a high level of polymorphism and shows biased use in protective antibody (Ab) responses to infections and vaccines. It is also highly expressed in several B cell malignancies and autoimmune diseases. G6 is an anti-idiotypic monoclonal Ab that selectively binds to IGHV1-6...
journal_title：Cell reports
pub_type： 杂志文章
doi：10.1016/j.celrep.2017.11.056
更新日期：2017-12-12 00:00:00
abstract：:The transcriptional response to infection with the bacterium Listeria monocytogenes (Lm) requires cooperative signals of the type I interferon (IFN-I)-stimulated JAK-STAT and proinflammatory NF-κB pathways. Using ChIP-seq analysis, we define genes induced in Lm-infected macrophages through synergistic transcriptional ...
journal_title：Cell reports
pub_type： 杂志文章
doi：10.1016/j.celrep.2015.06.021
更新日期：2015-07-14 00:00:00
abstract：:Information gained during goal pursuit motivates adaptive behavior. The anterior cingulate cortex (ACC) supports adaptive behavior, but how ACC signals are translated into motivational signals remains unclear. Rats with implants in the ACC and ventral tegmental area (VTA), a dopaminergic brain area implicated in motiv...
journal_title：Cell reports
pub_type： 杂志文章
doi：10.1016/j.celrep.2017.05.062
更新日期：2017-06-13 00:00:00
abstract：:Transcriptome analyses have revealed that convergent gene transcription can produce many 3'-overlapping mRNAs in diverse organisms. Few studies have examined the fate of 3'-complementary mRNAs in double-stranded RNA-dependent nuclear phenomena, and nothing is known about the cytoplasmic destiny of 3'-overlapping messe...
journal_title：Cell reports
pub_type： 杂志文章
doi：10.1016/j.celrep.2015.08.016
更新日期：2015-09-22 00:00:00
abstract：:CRISPR/Cas-based technologies have revolutionized genetic approaches to addressing a wide range of neurobiological questions. The ability of CRISPR/Cas to introduce mutations into target genes allows us to perform in vivo loss-of-function experiments without generating genetically engineered mice. However, the lack of...
journal_title：Cell reports
pub_type： 杂志文章
doi：10.1016/j.celrep.2019.06.038
更新日期：2019-07-09 00:00:00
abstract：:Transcription of developmental genes is controlled by multiple enhancers. Frequently, more than one enhancer can activate transcription from the same promoter in the same cells. How is regulatory information from multiple enhancers combined to determine the overall expression output? We measure nascent transcription d...
journal_title：Cell reports
pub_type： 杂志文章
doi：10.1016/j.celrep.2019.01.115
更新日期：2019-02-26 00:00:00
abstract：:The anorectic and weight-suppressive effects of growth differentiation factor-15 (GDF15) are attracting considerable attention for treating obesity. Current experiments in rats investigate whether GDF15 induces an aversive visceral malaise-based state that mediates its acute anorectic effect and, through aversion cond...
journal_title：Cell reports
pub_type： 杂志文章
doi：10.1016/j.celrep.2020.107543
更新日期：2020-04-21 00:00:00
abstract：:Remyelination is a multistep regenerative process that results in the reformation of myelin sheaths around demyelinated axons and is a critical therapeutic target. Here we show that immediate access to a running wheel following toxin-induced demyelination in mice enhances oligodendrogenesis, the rate of remyelination,...
journal_title：Cell reports
pub_type： 杂志文章
doi：10.1016/j.celrep.2018.08.060
更新日期：2018-09-18 00:00:00
abstract：:Gambogic acid (GA) is a natural compound derived from Chinese herbs that has been approved by the Chinese Food and Drug Administration for clinical trials in cancer patients; however, its molecular targets have not been thoroughly studied. Here, we report that GA inhibits tumor proteasome activity, with potency compar...
journal_title：Cell reports
pub_type： 杂志文章
doi：10.1016/j.celrep.2012.11.023
更新日期：2013-01-31 00:00:00
abstract：:Horizontal transmission of the microbiota between different individuals is widely used to normalize the microbiota in laboratory mice. However, little is known about the dynamics of microbial communities and the level of microbiota transmission after cohousing. We extensively analyzed the fecal microbiota in Jackson a...
journal_title：Cell reports
pub_type： 杂志文章
doi：10.1016/j.celrep.2019.05.042
更新日期：2019-06-11 00:00:00
abstract：:Adipocytes deficient in fatty acid synthase (iAdFASNKO) emit signals that mimic cold exposure to enhance the appearance of thermogenic beige adipocytes in mouse inguinal white adipose tissues (iWATs). Both cold exposure and iAdFASNKO upregulate the sympathetic nerve fiber (SNF) modulator Neuregulin 4 (Nrg4), activate ...
journal_title：Cell reports
pub_type： 杂志文章
doi：10.1016/j.celrep.2020.107998
更新日期：2020-08-04 00:00:00
abstract：:Brain plasticity is often restricted to critical periods in early life. Here, we show that a key regulator of this process in the visual cortex, Otx2 homeoprotein, is synthesized and secreted globally from the choroid plexus. Consequently, Otx2 is maintained in selected GABA cells unexpectedly throughout the mature fo...
journal_title：Cell reports
pub_type： 杂志文章
doi：10.1016/j.celrep.2013.05.014
更新日期：2013-06-27 00:00:00
abstract：:People tend to fall asleep when gently rocked or vibrated. Experimental studies have shown that rocking promotes sleep in humans and mice. However, the mechanisms underlying the phenomenon are not well understood. A habituation model proposes that habituation, a form of non-associative learning, mediates sleep inducti...
journal_title：Cell reports
pub_type： 杂志文章
doi：10.1016/j.celrep.2020.108462
更新日期：2020-12-01 00:00:00
abstract：:Breast cancer stem cells (BCSCs) play a critical role in tumor recurrence and metastasis. Exposure of breast cancer cells to chemotherapy leads to an enrichment of BCSCs. Here, we find that chemotherapy induces the expression of glutathione S-transferase omega 1 (GSTO1), which is dependent on hypoxia-inducible factor ...
journal_title：Cell reports
pub_type： 杂志文章
doi：10.1016/j.celrep.2017.02.001
更新日期：2017-02-21 00:00:00
abstract：:Endogenous retroviruses (ERVs), which make up 8% of the human genome, have been proposed to participate in the control of gene regulatory networks. In this study, we find a region- and developmental stage-specific expression pattern of ERVs in the developing human brain, which is linked to a transcriptional network ba...
journal_title：Cell reports
pub_type： 杂志文章
doi：10.1016/j.celrep.2016.12.010
更新日期：2017-01-03 00:00:00
abstract：:The architecture of renal glomeruli is acquired through intricate and still poorly understood developmental steps. In our study we identify a crucial glomerular morphogenetic event in nephrogenesis that drives the remodeling/separation of the prospective vascular pole (the future entrance of the glomerular arterioles)...
journal_title：Cell reports
pub_type： 杂志文章
doi：10.1016/j.celrep.2020.108304
更新日期：2020-10-27 00:00:00
abstract：:Viral persistence specifically inhibits CD4 Th1 responses and promotes Tfh immunity, but the mechanisms that suppress Th1 cells and the disease consequences of their loss are unclear. Here, we demonstrate that the loss of CD4 Th1 cells specifically leads to progressive CD8 T cell decline and dysfunction during viral p...
journal_title：Cell reports
pub_type： 杂志文章
doi：10.1016/j.celrep.2016.08.065
更新日期：2016-09-20 00:00:00
abstract：:Chromatin regulation is driven by multicomponent protein complexes, which form functional modules. Deciphering the components of these modules and their interactions is central to understanding the molecular pathways these proteins are regulating, their functions, and their relation to both normal development and dise...
journal_title：Cell reports
pub_type： 杂志文章
doi：10.1016/j.celrep.2014.05.050
更新日期：2014-07-10 00:00:00
abstract：:The MRE11-RAD50-NBS1 complex plays a central role in response to DNA double-strand breaks. Here, we identify a patient with bone marrow failure and developmental defects caused by biallelic RAD50 mutations. One of the mutations creates a null allele, whereas the other (RAD50E1035Δ) leads to the loss of a single residu...
journal_title：Cell reports
pub_type： 杂志文章
doi：10.1016/j.celrep.2020.108559
更新日期：2020-12-29 00:00:00
abstract：:Glycophosphatidylinositol-anchored proteins (GPI-APs) play essential roles in physiology, but their biogenesis and trafficking have not been systematically characterized. Here, we took advantage of the recently available haploid genetics approach to dissect GPI-AP pathways in human cells using prion protein (PrP) and ...
journal_title：Cell reports
pub_type： 杂志文章
doi：10.1016/j.celrep.2015.05.026
更新日期：2015-06-23 00:00:00
abstract：:Proprioception, the sense of limb and body position, is essential for generating proper movement. Unconscious proprioceptive information travels through cerebellar-projecting neurons in the spinal cord and medulla. The progenitor domain defined by the basic-helix-loop-helix (bHLH) transcription factor, ATOH1, has been...
journal_title：Cell reports
pub_type： 杂志文章
doi：10.1016/j.celrep.2015.09.064
更新日期：2015-11-10 00:00:00
abstract：:The use of retinal organoids requires efficient differentiation from induced pluripotent stem cells (iPSCs). In this issue of Cell Reports, Wang et al. (2018) examine how the chromatin landscape after iPSC programming predicts their ability to differentiate into retinal tissue. ...
journal_title：Cell reports
pub_type： 杂志文章
doi：10.1016/j.celrep.2018.02.078
更新日期：2018-03-06 00:00:00
abstract：:Graft-versus-host disease (GVHD) limits the success of allogeneic hematopoietic cell transplantation (allo-HCT). Lysosomal acid lipase (LAL) mediates the intrinsic lipolysis of cells to generate free fatty acids (FFAs), which play an essential role in the development, proliferation, and function of T cells. Here, we f...
journal_title：Cell reports
pub_type： 杂志文章
doi：10.1016/j.celrep.2020.108316
更新日期：2020-10-27 00:00:00
abstract：:Nonalcoholic fatty liver disease is the most common chronic liver disorder in developed countries. Its pathogenesis is poorly understood, and therapeutic options are limited. Here, we show that SIRT7, an NAD(+)-dependent H3K18Ac deacetylase, functions at chromatin to suppress ER stress and prevent the development of f...
journal_title：Cell reports
pub_type： 杂志文章
doi：10.1016/j.celrep.2013.10.007
更新日期：2013-11-14 00:00:00
