Abstract:
:Communication between organelles plays key roles in cell biology. In particular, physical and functional coupling of the endoplasmic reticulum (ER) and mitochondria is crucial for regulation of various physiological and pathophysiological processes. Here, we demonstrate that Presenilin 2 (PS2), mutations in which underlie familial Alzheimer's disease (FAD), promotes ER-mitochondria coupling only in the presence of mitofusin 2 (Mfn2). PS2 is not necessary for the antagonistic effect of Mfn2 on organelle coupling, although its abundance can tune it. The two proteins physically interact, whereas their homologues Mfn1 and PS1 are dispensable for this interplay. Moreover, PS2 mutants associated with FAD are more effective than the wild-type form in modulating ER-mitochondria tethering because their binding to Mfn2 in mitochondria-associated membranes is favored. We propose a revised model for ER-mitochondria interaction to account for these findings and discuss possible implications for FAD pathogenesis.
journal_name
Cell Repjournal_title
Cell reportsauthors
Filadi R,Greotti E,Turacchio G,Luini A,Pozzan T,Pizzo Pdoi
10.1016/j.celrep.2016.05.013subject
Has Abstractpub_date
2016-06-07 00:00:00pages
2226-2238issue
10issn
2211-1247pii
S2211-1247(16)30580-0journal_volume
15pub_type
杂志文章相关文献
Cell Reports文献大全abstract::Most aging hypotheses assume the accumulation of damage, resulting in gradual physiological decline and, ultimately, death. Avoiding protein damage accumulation by enhanced turnover should slow down the aging process and extend the lifespan. However, lowering translational efficiency extends rather than shortens the l...
journal_title:Cell reports
pub_type: 杂志文章
doi:10.1016/j.celrep.2016.07.088
更新日期:2016-09-13 00:00:00
abstract::Neurons exhibit dynamic structural changes in response to extracellular stimuli. Microtubules (MTs) provide rapid and dramatic cytoskeletal changes within the structural framework. However, the molecular mechanisms and signaling networks underlying MT dynamics remain unknown. Here, we have applied a comprehensive and ...
journal_title:Cell reports
pub_type: 杂志文章
doi:10.1016/j.celrep.2015.08.018
更新日期:2015-09-22 00:00:00
abstract::Here, we ask how neural stem cells (NSCs) transition in the developing neocortex from a rapidly to a slowly proliferating state, a process required to maintain lifelong stem cell pools. We identify LRIG1, known to regulate receptor tyrosine kinase signaling in other cell types, as a negative regulator of cortical NSC ...
journal_title:Cell reports
pub_type: 杂志文章
doi:10.1016/j.celrep.2020.108257
更新日期:2020-10-13 00:00:00
abstract::Antibodies secreted within the intestinal tract provide protection from the invasion of microbes into the host tissues. Germinal center (GC) formation in lymph nodes and spleen strictly requires SLAM-associated protein (SAP)-mediated T cell functions; however, it is not known whether this mechanism plays a similar rol...
journal_title:Cell reports
pub_type: 杂志文章
doi:10.1016/j.celrep.2020.01.032
更新日期:2020-02-11 00:00:00
abstract::The relationship between the host and its microbiota is challenging to understand because both microbial communities and their environments are highly variable. We have developed a set of techniques based on population dynamics and information theory to address this challenge. These methods identify additional bacteri...
journal_title:Cell reports
pub_type: 杂志文章
doi:10.1016/j.celrep.2015.12.088
更新日期:2016-02-02 00:00:00
abstract::Many infections are caused by pathogens that are similar, but not identical, to previously encountered viruses, bacteria, or vaccines. In such re-infections, pathogens introduce known antigens, which are recognized by memory T cells and new antigens that activate naive T cells. How preexisting memory T cells impact th...
journal_title:Cell reports
pub_type: 杂志文章
doi:10.1016/j.celrep.2016.09.072
更新日期:2016-10-11 00:00:00
abstract::Antimetabolites that affect nucleotide metabolism are frontline chemotherapy agents in several cancers and often successfully target one carbon metabolism. However, the precise mechanisms and resulting determinants of their therapeutic value are unknown. We show that 5-fluorouracil (5-FU), a commonly used antimetaboli...
journal_title:Cell reports
pub_type: 杂志文章
doi:10.1016/j.celrep.2016.05.035
更新日期:2016-06-14 00:00:00
abstract::Epithelial tissues, such as the skin, rely on cellular plasticity of stem cells (SCs) from different niches to restore tissue function after injury. How these molecularly and functionally diverse SC populations respond to injury remains elusive. Here, we genetically labeled Lgr5- or Lgr6-expressing cells from the hair...
journal_title:Cell reports
pub_type: 杂志文章
doi:10.1016/j.celrep.2018.09.059
更新日期:2018-10-16 00:00:00
abstract::Bromodomain and extra-terminal domain (BET) family inhibitors offer an approach to treating hematological malignancies. We used precision nuclear run-on transcription sequencing (PRO-seq) to create high-resolution maps of active RNA polymerases across the genome in t(8;21) acute myeloid leukemia (AML), as these polyme...
journal_title:Cell reports
pub_type: 杂志文章
doi:10.1016/j.celrep.2016.07.032
更新日期:2016-08-16 00:00:00
abstract::In contrast to our extensive knowledge on covalent small ubiquitin-like modifier (SUMO) target proteins, we are limited in our understanding of non-covalent SUMO-binding proteins. We identify interactors of different SUMO isoforms-monomeric SUMO1, monomeric SUMO2, or linear trimeric SUMO2 chains-using a mass spectrome...
journal_title:Cell reports
pub_type: 杂志文章
doi:10.1016/j.celrep.2021.108691
更新日期:2021-01-26 00:00:00
abstract::Sex determination is a unique process that allows the study of multipotent progenitors and their acquisition of sex-specific fates during differentiation of the gonad into a testis or an ovary. Using time series single-cell RNA sequencing (scRNA-seq) on ovarian Nr5a1-GFP+ somatic cells during sex determination, we ide...
journal_title:Cell reports
pub_type: 杂志文章
doi:10.1016/j.celrep.2019.02.069
更新日期:2019-03-19 00:00:00
abstract::Pneumonias caused by influenza A virus (IAV) co- and secondary bacterial infections are characterized by their severity and high mortality rate. Previously, we have shown that bacterial pore-forming toxin (PFT)-mediated necroptosis is a key driver of acute lung injury during bacterial pneumonia. Here, we evaluate the ...
journal_title:Cell reports
pub_type: 杂志文章
doi:10.1016/j.celrep.2020.108062
更新日期:2020-08-25 00:00:00
abstract::Thymic epithelial cells (TECs) are critically required for T cell development, but the cellular mechanisms that maintain adult TECs are poorly understood. Here, we show that a previously unidentified subpopulation, EpCam(+)UEA1(-)Ly-51(+)PLET1(+)MHC class II(hi), which comprises <0.5% of adult TECs, contains bipotent ...
journal_title:Cell reports
pub_type: 杂志文章
doi:10.1016/j.celrep.2016.02.080
更新日期:2016-03-29 00:00:00
abstract::Recent rapid progress in the field of mechanobiology has been driven by novel emerging tools and methodologies and growing interest from different scientific disciplines. Specific progress has been made toward understanding how cell mechanics is linked to intracellular signaling and the regulation of gene expression i...
journal_title:Cell reports
pub_type: 杂志文章,评审
doi:10.1016/j.celrep.2019.08.075
更新日期:2019-10-01 00:00:00
abstract::Obesity is associated with colon cancer pathogenesis, but the underlying mechanism is actively debated. Here, we confirm that diet-induced obesity promotes tumor growth in two murine colon cancer models and show that this effect is reversed by an orally administered controlled-release mitochondrial protonophore (CRMP)...
journal_title:Cell reports
pub_type: 杂志文章
doi:10.1016/j.celrep.2018.06.008
更新日期:2018-07-03 00:00:00
abstract::Endophilin-A, a well-characterized endocytic adaptor essential for synaptic vesicle recycling, has recently been linked to neurodegeneration. We report here that endophilin-A deficiency results in impaired movement, age-dependent ataxia, and neurodegeneration in mice. Transcriptional analysis of endophilin-A mutant mi...
journal_title:Cell reports
pub_type: 杂志文章
doi:10.1016/j.celrep.2016.09.058
更新日期:2016-10-18 00:00:00
abstract::The neurodevelopmental origin of hyperactivity disorder has been suggested to involve the dopaminergic system, but the underlying mechanisms are still unknown. Here, transcription factors Lmx1a and Lmx1b are shown to be essential for midbrain dopaminergic (mDA) neuron excitatory synaptic inputs and dendritic developme...
journal_title:Cell reports
pub_type: 杂志文章
doi:10.1016/j.celrep.2020.01.084
更新日期:2020-02-18 00:00:00
abstract::Glucose-dependent insulinotropic polypeptide (GIP) is an incretin hormone involved in nutrient homeostasis. GIP receptor (GIPR) is constitutively internalized and returned to the plasma membrane, atypical behavior for a G-protein-coupled receptor (GPCR). GIP promotes GIPR downregulation from the plasma membrane by inh...
journal_title:Cell reports
pub_type: 杂志文章
doi:10.1016/j.celrep.2016.11.050
更新日期:2016-12-13 00:00:00
abstract::SUMOylation has been implicated in cellular stress adaptation, but its role in regulating liver kinase B1 (LKB1), a major upstream kinase of the energy sensor AMP-activated protein kinase (AMPK), is unknown. Here, we show that energy stress triggers an increase in SUMO1 modification of LKB1, despite a global reduction...
journal_title:Cell reports
pub_type: 杂志文章
doi:10.1016/j.celrep.2015.07.002
更新日期:2015-08-04 00:00:00
abstract::Durable humoral immunity against epidemic infectious disease requires the survival of long-lived plasma cells (LLPCs). LLPC longevity is dependent on metabolic programs distinct from short-lived plasma cells (SLPCs); however, the mechanistic basis for this difference is unclear. We have previously shown that CD28, the...
journal_title:Cell reports
pub_type: 杂志文章
doi:10.1016/j.celrep.2020.107815
更新日期:2020-06-23 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::Atrophy of neurons in the prefrontal cortex (PFC) plays a key role in the pathophysiology of depression and related disorders. The ability to promote both structural and functional plasticity in the PFC has been hypothesized to underlie the fast-acting antidepressant properties of the dissociative anesthetic ketamine....
journal_title:Cell reports
pub_type: 杂志文章
doi:10.1016/j.celrep.2018.05.022
更新日期:2018-06-12 00:00:00
abstract::CD4+ Foxp3+ T regulatory (Treg) cells are key players in preventing lethal autoimmunity. Tregs undertake differentiation processes and acquire diverse functional properties. However, how Treg's differentiation and functional specification are regulated remains incompletely understood. Here, we report that gradient exp...
journal_title:Cell reports
pub_type: 杂志文章
doi:10.1016/j.celrep.2019.05.061
更新日期:2019-06-18 00:00:00
abstract::The ability of cells to stably maintain their fate is governed by specific transcription regulators. Here, we show that the Scalloped (Sd) and Nervous fingers-1 (Nerfin-1) transcription factors physically and functionally interact to maintain medulla neuron fate in the Drosophila melanogaster CNS. Using Targeted DamID...
journal_title:Cell reports
pub_type: 杂志文章
doi:10.1016/j.celrep.2018.10.038
更新日期:2018-11-06 00:00:00
abstract::The proneural transcription factor Ascl1 coordinates gene expression in both proliferating and differentiating progenitors along the neuronal lineage. Here, we used a cellular model of neurogenesis to investigate how Ascl1 interacts with the chromatin landscape to regulate gene expression when promoting neuronal diffe...
journal_title:Cell reports
pub_type: 杂志文章
doi:10.1016/j.celrep.2015.02.025
更新日期:2015-03-10 00:00:00
abstract::Oxytocin is a hormone with various actions. Oxytocin-containing parvocellular neurons project to the brainstem and spinal cord. Oxytocin release from these neurons suppresses nociception of inflammatory pain, the molecular mechanism of which remains unclear. Here, we report that the noxious stimulus receptor TRPV1 is ...
journal_title:Cell reports
pub_type: 杂志文章
doi:10.1016/j.celrep.2017.10.063
更新日期:2017-11-07 00:00:00
abstract::The E3 ubiquitin ligase HUWE1, deregulated in carcinoma, has been implicated in tumor formation. Here, we uncover a role for HUWE1 in cell migration and invasion through degrading the RAC activator TIAM1, implying an additional function in malignant progression. In MDCKII cells in response to HGF, HUWE1 catalyzes TIAM...
journal_title:Cell reports
pub_type: 杂志文章
doi:10.1016/j.celrep.2014.12.012
更新日期:2015-01-06 00:00:00
abstract::Many animals fight for dominance between conspecifics. Because winners could obtain more resources than losers, fighting outcomes are important for the animal's survival, especially in a situation with insufficient resources, such as hunger. However, it remains unclear whether and how hunger affects fighting outcomes....
journal_title:Cell reports
pub_type: 杂志文章
doi:10.1016/j.celrep.2020.107790
更新日期:2020-06-23 00:00:00
abstract::Ring NTPases are a class of ubiquitous molecular motors involved in basic biological partitioning processes. dsDNA viruses encode ring ATPases that translocate their genomes to near-crystalline densities within pre-assembled viral capsids. Here, X-ray crystallography, cryoEM, and biochemical analyses of the dsDNA pack...
journal_title:Cell reports
pub_type: 杂志文章
doi:10.1016/j.celrep.2016.01.058
更新日期:2016-03-01 00:00:00
abstract::Pancreatic α cells may process proglucagon not only to glucagon but also to glucagon-like peptide-1 (GLP-1). However, the biological relevance of paracrine GLP-1 for β cell function remains unclear. We studied effects of locally derived insulin secretagogues on β cell function and glucose homeostasis using mice with α...
journal_title:Cell reports
pub_type: 杂志文章
doi:10.1016/j.celrep.2017.03.005
更新日期:2017-03-28 00:00:00