Abstract：
:Clec16a has been identified as a disease susceptibility gene for type 1 diabetes, multiple sclerosis, and adrenal dysfunction, but its function is unknown. Here we report that Clec16a is a membrane-associated endosomal protein that interacts with E3 ubiquitin ligase Nrdp1. Loss of Clec16a leads to an increase in the Nrdp1 target Parkin, a master regulator of mitophagy. Islets from mice with pancreas-specific deletion of Clec16a have abnormal mitochondria with reduced oxygen consumption and ATP concentration, both of which are required for normal β cell function. Indeed, pancreatic Clec16a is required for normal glucose-stimulated insulin release. Moreover, patients harboring a diabetogenic SNP in the Clec16a gene have reduced islet Clec16a expression and reduced insulin secretion. Thus, Clec16a controls β cell function and prevents diabetes by controlling mitophagy. This pathway could be targeted for prevention and control of diabetes and may extend to the pathogenesis of other Clec16a- and Parkin-associated diseases.
journal_name
Celljournal_title
Cellauthors
Soleimanpour SA,Gupta A,Bakay M,Ferrari AM,Groff DN,Fadista J,Spruce LA,Kushner JA,Groop L,Seeholzer SH,Kaufman BA,Hakonarson H,Stoffers DAdoi
10.1016/j.cell.2014.05.016subject
Has Abstractpub_date
2014-06-19 00:00:00pages
1577-90issue
7eissn
0092-8674issn
1097-4172pii
S0092-8674(14)00657-6journal_volume
157pub_type
杂志文章相关文献
CELL文献大全abstract：:We have adopted Drosophila tissue culture cells as a host system for studying the structure and function of mammalian transcription factors. These cells provide an Sp1-deficient background and have been used in a complementation assay to identify functional domains of human transcription factor Sp1. The SV40 early pro...
journal_title：Cell
pub_type： 杂志文章
doi：10.1016/0092-8674(88)90144-4
更新日期：1988-12-02 00:00:00
abstract：:The transition from the juvenile to the adult phase of shoot development in plants is accompanied by changes in vegetative morphology and an increase in reproductive potential. Here, we describe the regulatory mechanism of this transition. We show that miR156 is necessary and sufficient for the expression of the juven...
journal_title：Cell
pub_type： 杂志文章
doi：10.1016/j.cell.2009.06.031
更新日期：2009-08-21 00:00:00
abstract：:The TDS4 gene of S. cerevisiae was isolated as an allele-specific high copy suppressor of mutations within the basic region of the TATA-binding protein (TBP). The gene is essential for viability and encodes a 596 aa protein. The first 300 aa of the TDS4 protein exhibit significant sequence similarity to the RNA polyme...
journal_title：Cell
pub_type： 杂志文章
doi：10.1016/0092-8674(92)90351-c
更新日期：1992-10-16 00:00:00
abstract：:The v-erbB gene of avian erythroblastosis virus (AEV) codes for an integral plasma membrane glycoprotein, gp74erbB. Expression of gp74erbB and its intracellular precursors, gp66erbB and gp68erbB, has been studied in cells transformed by two temperature-sensitive mutants of AEV. After shift to 42 degrees C, the process...
journal_title：Cell
pub_type： 杂志文章
doi：10.1016/0092-8674(84)90046-1
更新日期：1984-04-01 00:00:00
abstract：:The 10Sa RNA, encoded by the E. coli ssrA gene, appears to modulate action of some DNA-binding proteins. When ssrA is inactivated, lacZ expression from the lac operon, as well as galK from a gal operon fused to a phage lambda promoter, is reduced from that observed in bacteria wild-type for ssrA. These differences are...
journal_title：Cell
pub_type： 杂志文章
doi：10.1016/0092-8674(95)90164-7
更新日期：1995-10-20 00:00:00
abstract：:We have developed an in vitro system utilizing yeast cell-free extracts to catalyze recombination events between homologous plasmids containing different mutant alleles of the Tet or ARG4 genes. The reaction increased the frequency of Tcr or Arg+ transformants (recombinants) from 2 X 10(-6) to 1-3 X 10(-3). Linearizin...
journal_title：Cell
pub_type： 杂志文章
doi：10.1016/0092-8674(83)90113-7
更新日期：1983-12-01 00:00:00
abstract：:Cytotoxic brain edema triggered by neuronal swelling is the chief cause of mortality following brain trauma and cerebral infarct. Using fluorescence lifetime imaging to analyze contributions of intracellular ionic changes in brain slices, we find that intense Na(+) entry triggers a secondary increase in intracellular ...
journal_title：Cell
pub_type： 杂志文章
doi：10.1016/j.cell.2015.03.029
更新日期：2015-04-23 00:00:00
abstract：:mRNA made in eukaryotic cells typically has a 3' poly(A) tail that is added posttranscriptionally. To investigate mechanisms by which 3' poly(A) is formed, we identified the genes for the two vaccina virus-encoded polypeptides, VP55 and VP39. Primer-dependent polyadenylation activity was associated exclusively with pu...
journal_title：Cell
pub_type： 杂志文章
doi：10.1016/0092-8674(91)90048-4
更新日期：1991-09-20 00:00:00
abstract：:The fluid-mosaic model posits a liquid-like plasma membrane, which can flow in response to tension gradients. It is widely assumed that membrane flow transmits local changes in membrane tension across the cell in milliseconds, mediating long-range signaling. Here, we show that propagation of membrane tension occurs qu...
journal_title：Cell
pub_type： 杂志文章
doi：10.1016/j.cell.2018.09.054
更新日期：2018-12-13 00:00:00
abstract：:It was previously demonstrated that the 60,000 dalton (p60) precursor-like polyprotein containing murine p30 was a constituent of the feline leukemia virus pseudotype of Moloney sarcoma virus [m1MSV(FeLV)]. It is now shown that p60 is detected in cells of five mammalian species transformed by m1MSV, indicating that p...
journal_title：Cell
pub_type： 杂志文章
doi：10.1016/0092-8674(77)90142-8
更新日期：1977-01-01 00:00:00
abstract：:The detection and discrimination of odorants in mammals is thought to be mediated by a family of 100-1000 seven transmembrane domain receptor proteins, although none of these putative olfactory receptors have been shown to bind individual odorants with high affinity. We have used a genetic approach to identify the gen...
journal_title：Cell
pub_type： 杂志文章
doi：10.1016/0092-8674(95)90118-3
更新日期：1995-11-03 00:00:00
abstract：:The HIV-1 matrix (MA) protein contains two subcellular localization signals with opposing effects. A myristoylated N-terminus governs particle assembly at the plasma membrane, and a nucleophilic motif facilitates import of the viral preintegration complex into the nucleus of nondividing cells. Here, we show that myris...
journal_title：Cell
pub_type： 杂志文章
doi：10.1016/0092-8674(95)90488-3
更新日期：1995-02-10 00:00:00
abstract：:Secreted proteins of the Wnt family have profound organizing roles during animal development and are transduced via the activities of the Frizzled (Fz) class of transmembrane receptors and the TCF/LEF/Pangolin class of transcription factors. beta-catenins, including Drosophila Armadillo (Arm), link activation of Fz at...
journal_title：Cell
pub_type： 杂志文章,收录出版
doi：10.1016/s0092-8674(02)01037-1
更新日期：2002-10-18 00:00:00
abstract：:TFIIH is a multisubunit protein complex that plays an essential role in nucleotide excision repair and transcription of protein-coding genes. Here, we report that TFIIH is also required for ribosomal RNA synthesis in vivo and in vitro. In yeast, pre-rRNA synthesis is impaired in TFIIH ts strains. In a mouse, part of c...
journal_title：Cell
pub_type： 杂志文章
doi：10.1016/s0092-8674(02)00729-8
更新日期：2002-05-03 00:00:00
abstract：:Neurons need to alter their response to a given stimulus over time in order for the animal to modify its behavior within a changing environment. Chen et al. now demonstrate that neuronal structure and function are altered coordinately by the history of the cell's activity through an unexpected molecular pathway. ...
journal_title：Cell
pub_type： 评论,杂志文章
doi：10.1016/j.cell.2012.09.008
更新日期：2012-09-28 00:00:00
abstract：:The small ribonucleoproteins recognized by anti-La autoantibodies contain a heterogeneous mixture of small RNAs from uninfected mammalian cells. The identity of many of these has now been established by the discovery of precursor forms of 5S rRNA and of certain tRNAs among La RNAs from HeLa cells. The small fraction o...
journal_title：Cell
pub_type： 杂志文章
doi：10.1016/0092-8674(82)90099-x
更新日期：1982-05-01 00:00:00
abstract：:The erythropoietin receptor (EpoR) is essential for production of red blood cells; a principal function of EpoR is to rescue committed erythroid progenitors from apoptosis. Stat5 is rapidly activated following EpoR stimulation, but its function in erythropoiesis has been unclear since adult Stat5a-/-5b-/- mice have no...
journal_title：Cell
pub_type： 杂志文章
doi：10.1016/s0092-8674(00)81013-2
更新日期：1999-07-23 00:00:00
abstract：:Recently, a Drosophila gene has been identified, extradenticle, whose product modulates the morphological consequences of homeotic selector genes. We show here that extradenticle protein raises the DNA binding specificity of Ultrabithorax and abdominal-A but not that of Abdominal-B. We further show that extradenticle ...
journal_title：Cell
pub_type： 杂志文章
doi：10.1016/0092-8674(94)90526-6
更新日期：1994-08-26 00:00:00
abstract：:New biological tools provide new techniques to probe fundamental biological processes. Here we describe the burgeoning field of proteolysis-targeting chimeras (PROTACs), which are capable of modulating protein concentrations at a post-translational level by co-opting the ubiquitin-proteasome system. We describe the PR...
journal_title：Cell
pub_type： 杂志文章,评审
doi：10.1016/j.cell.2019.11.031
更新日期：2020-04-02 00:00:00
abstract：:We find that inactivation of a Drosophila homolog of the tumor suppressor APC (D-APC) causes retinal neuronal degeneration and pigment cell hypertrophy, a phenotype remarkably similar to that found in humans with germline APC mutations. Retinal degeneration in the D-APC mutant results from apoptotic cell death, which ...
journal_title：Cell
pub_type： 杂志文章
doi：10.1016/s0092-8674(00)81461-0
更新日期：1998-06-26 00:00:00
abstract：:The cellular complexity and scale of the early liver have constrained analyses examining its emergence during organogenesis. To circumvent these issues, we analyzed 45,334 single-cell transcriptomes from embryonic day (E)7.5, when endoderm progenitors are specified, to E10.5 liver, when liver parenchymal and non-paren...
journal_title：Cell
pub_type： 杂志文章
doi：10.1016/j.cell.2020.09.012
更新日期：2020-10-29 00:00:00
abstract：:We have determined the complete 9202 nucleotide sequence of the visna lentivirus. The deduced genetic organization most closely resembles that of the AIDS retrovirus in that there is a novel central region separating pol and env. Moreover, there is a close phylogenetic relationship between the conserved reverse transc...
journal_title：Cell
pub_type： 杂志文章
doi：10.1016/s0092-8674(85)80132-x
更新日期：1985-08-01 00:00:00
abstract：:We have investigated the in vivo functional role of rab5, a small GTPase associated with the plasma membrane and early endosomes. Wild-type rab5 or rab5-ile133, a mutant protein defective in GTP binding, was overexpressed in baby hamster kidney cells. In cells expressing the rab5ile 133 protein, the rate of endocytosi...
journal_title：Cell
pub_type： 杂志文章
doi：10.1016/0092-8674(92)90306-w
更新日期：1992-09-04 00:00:00
abstract：:Maintenance of a constant cell volume in response to extracellular or intracellular osmotic changes is critical for cellular homeostasis. Activation of a ubiquitous volume-regulated anion channel (VRAC) plays a key role in this process; however, its molecular identity in vertebrates remains unknown. Here, we used a ce...
journal_title：Cell
pub_type： 杂志文章
doi：10.1016/j.cell.2014.03.024
更新日期：2014-04-10 00:00:00
abstract：:Glial cells are essential components of the nervous system. In this issue, Singhvi et al. uncover cellular and molecular mechanisms through which C. elegans glia shape sensory neuron terminals and thus control animal thermosensing behaviors. ...
journal_title：Cell
pub_type： 评论,杂志文章
doi：10.1016/j.cell.2016.04.052
更新日期：2016-05-05 00:00:00
abstract：:The mitochondrial unfolded protein response (UPRmt) can be triggered in a cell-non-autonomous fashion across multiple tissues in response to mitochondrial dysfunction. The ability to communicate information about the presence of mitochondrial stress enables a global response that can ultimately better protect an organ...
journal_title：Cell
pub_type： 杂志文章
doi：10.1016/j.cell.2018.06.029
更新日期：2018-08-09 00:00:00
abstract：:We present a strategy for generating and analyzing comprehensive genetic-interaction maps, termed E-MAPs (epistatic miniarray profiles), comprising quantitative measures of aggravating or alleviating interactions between gene pairs. Crucial to the interpretation of E-MAPs is their high-density nature made possible by ...
journal_title：Cell
pub_type： 杂志文章
doi：10.1016/j.cell.2005.08.031
更新日期：2005-11-04 00:00:00
abstract：:Treating B16 mouse melanoma cells with monoclonal antibody NORM-2 reduces cell growth in tissue culture, agar, and syngeneic mice. We show that the NORM-2 antibody recognizes an integral 83 kd glycoprotein that is mobile in the plane of the plasma membrane of B16 melanoma cells. Expression of the glycoprotein is reduc...
journal_title：Cell
pub_type： 杂志文章
doi：10.1016/0092-8674(86)90510-6
更新日期：1986-12-05 00:00:00
abstract：:The 2013-2015 West African epidemic of Ebola virus disease (EVD) reminds us of how little is known about biosafety level 4 viruses. Like Ebola virus, Lassa virus (LASV) can cause hemorrhagic fever with high case fatality rates. We generated a genomic catalog of almost 200 LASV sequences from clinical and rodent reserv...
journal_title：Cell
pub_type： 杂志文章
doi：10.1016/j.cell.2015.07.020
更新日期：2015-08-13 00:00:00
abstract：:The interplay of genetics and the environment in the etiology of Alzheimer's disease (AD) is not well understood. Now, Lazarov and coworkers show that a simple paradigm of environmental enrichment alleviates amyloid burden and alters disease-associated gene expression changes in a double transgenic mouse model of AD. ...
journal_title：Cell
pub_type： 评论,杂志文章,评审
doi：10.1016/j.cell.2005.02.027
更新日期：2005-03-11 00:00:00
