Abstract:
:Neurons face the challenge of maintaining cellular homeostasis through lysosomal degradation. While enzymatically active degradative lysosomes are enriched in the soma, their axonal trafficking and positioning and impact on axonal physiology remain elusive. Here, we characterized axon-targeted delivery of degradative lysosomes by applying fluorescent probes that selectively label active forms of lysosomal cathepsins D, B, L, and GCase. By time-lapse imaging of cortical neurons in microfluidic devices and standard dishes, we reveal that soma-derived degradative lysosomes rapidly influx into distal axons and target to autophagosomes and Parkinson disease-related α-synuclein cargos for local degradation. Impairing lysosome axonal delivery induces an aberrant accumulation of autophagosomes and α-synuclein cargos in distal axons. Our study demonstrates that the axon is an active compartment for local degradation and reveals fundamental aspects of axonal lysosomal delivery and maintenance. Our work establishes a foundation for investigations into axonal lysosome trafficking and functionality in neurodegenerative diseases.
journal_name
Cell Repjournal_title
Cell reportsauthors
Farfel-Becker T,Roney JC,Cheng XT,Li S,Cuddy SR,Sheng ZHdoi
10.1016/j.celrep.2019.06.013subject
Has Abstractpub_date
2019-07-02 00:00:00pages
51-64.e4issue
1issn
2211-1247pii
S2211-1247(19)30771-5journal_volume
28pub_type
杂志文章相关文献
Cell Reports文献大全abstract::Senescence is a cellular response preventing tumorigenesis. The Ras oncogene is frequently activated or mutated in human cancers, but Ras activation is insufficient to transform primary cells. In a search for cooperating oncogenes, we identify the lysine demethylase JMJD2A/KDM4A. We show that JMJD2A functions as a neg...
journal_title:Cell reports
pub_type: 杂志文章
doi:10.1016/j.celrep.2012.09.033
更新日期:2012-11-29 00:00:00
abstract::Residual cell-intrinsic innate immunity in cancer cells hampers infection with oncolytic viruses. Translational control of mRNA is an important feature of innate immunity, yet the identity of translationally regulated mRNAs functioning in host defense remains ill-defined. We report the translatomes of resistant murine...
journal_title:Cell reports
pub_type: 杂志文章
doi:10.1016/j.celrep.2019.11.072
更新日期:2019-12-17 00:00:00
abstract::Mutations in CEP290, a transition zone protein in primary cilia, cause diverse ciliopathies, including Leber congenital amaurosis (LCA) and Joubert-syndrome and related disorders (JSRD). We examined cilia biogenesis and function in cells derived from CEP290-LCA and CEP290-JSRD patients. CEP290 protein was reduced in L...
journal_title:Cell reports
pub_type: 杂志文章
doi:10.1016/j.celrep.2017.06.045
更新日期:2017-07-11 00:00:00
abstract::Human cells contain five canonical, replication-dependent somatic histone H1 subtypes (H1.1, H1.2, H1.3, H1.4, and H1.5). Although they are key chromatin components, the genomic distribution of the H1 subtypes is still unknown, and their role in chromatin processes has thus far remained elusive. Here, we map the genom...
journal_title:Cell reports
pub_type: 杂志文章
doi:10.1016/j.celrep.2013.05.003
更新日期:2013-06-27 00:00:00
abstract::Mutation hotspots and showers occur across phylogeny and profoundly influence genome evolution, yet the mechanisms that produce hotspots remain obscure. We report that DNA double-strand breaks (DSBs) provoke mutation hotspots via stress-induced mutation in Escherichia coli. With tet reporters placed 2 kb to 2 Mb (half...
journal_title:Cell reports
pub_type: 杂志文章
doi:10.1016/j.celrep.2012.08.033
更新日期:2012-10-25 00:00:00
abstract::Recent reports suggest that botulinum neurotoxin (BoNT) A, which is widely used clinically to inhibit neurotransmission, can spread within networks of neurons to have distal effects, but this remains controversial. Moreover, it is not known whether other members of this toxin family are transferred between neurons. He...
journal_title:Cell reports
pub_type: 杂志文章
doi:10.1016/j.celrep.2016.06.104
更新日期:2016-08-16 00:00:00
abstract::In mammalian skin, Merkel cells are mechanoreceptor cells that are required for the perception of gentle touch. Recent evidence indicates that mature Merkel cells descend from the proliferative layer of skin epidermis; however, the stem cell niche for Merkel cell homeostasis has not been reported. Here, we provide gen...
journal_title:Cell reports
pub_type: 杂志文章
doi:10.1016/j.celrep.2013.04.026
更新日期:2013-06-27 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::The corpus callosum is the major axon tract that connects and integrates neural activity between the two cerebral hemispheres. Although ∼1:4,000 children are born with developmental absence of the corpus callosum, the primary etiology of this condition remains unknown. Here, we demonstrate that midline crossing of cal...
journal_title:Cell reports
pub_type: 杂志文章
doi:10.1016/j.celrep.2016.09.033
更新日期:2016-10-11 00:00:00
abstract::Dentate gyrus (DG) development requires specification of granule cell (GC) progenitors in the hippocampal neuroepithelium, as well as their proliferation and migration into the primordial DG. We identify the Plexin family members Plxna2 and Plxna4 as important regulators of DG development. Distribution of immature GCs...
journal_title:Cell reports
pub_type: 杂志文章
doi:10.1016/j.celrep.2017.12.044
更新日期:2018-01-09 00:00:00
abstract::Tumor suppressor p53 regulates transcription of stress-response genes. Many p53 targets remain undiscovered because of uncertainty as to where p53 binds in the genome and the fact that few genes reside near p53-bound recognition elements (REs). Using chromatin immunoprecipitation followed by exonuclease treatment (ChI...
journal_title:Cell reports
pub_type: 杂志文章
doi:10.1016/j.celrep.2014.06.030
更新日期:2014-07-24 00:00:00
abstract::At presynaptic active zones, exocytosis of neurotransmitter vesicles (SVs) is driven by SNARE complexes that recruit Syb2 and SNAP25. However, it remains unknown which SNAREs promote the secretion of neuronal proteins, including those essential for circuit development and experience-dependent plasticity. Here we demon...
journal_title:Cell reports
pub_type: 杂志文章
doi:10.1016/j.celrep.2015.04.032
更新日期:2015-05-19 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::Bat cells and tissue have elevated basal expression levels of antiviral genes commonly associated with interferon alpha (IFNα) signaling. Here, we show Interferon Regulatory Factor 1 (IRF1), 3, and 7 levels are elevated in most bat tissues and that, basally, IRFs contribute to the expression of type I IFN ligands and ...
journal_title:Cell reports
pub_type: 杂志文章
doi:10.1016/j.celrep.2020.108345
更新日期:2020-11-03 00:00:00
abstract::The development of an embryo requires precise spatiotemporal regulation of cellular processes. During Drosophila gastrulation, a precise temporal pattern of cell division is encoded through transcriptional regulation of cdc25(string) in 25 distinct mitotic domains. Using a genetic screen, we demonstrate that the same ...
journal_title:Cell reports
pub_type: 杂志文章
doi:10.1016/j.celrep.2016.08.034
更新日期:2016-09-13 00:00:00
abstract::The role of CD4+ T cells in the ischemic tissues of T2D patients remains unclear. Here, we report that T2D patients' vascular density was negatively correlated with the number of infiltrating CD4+ T cells after ischemic injury. Th1 was the predominant subset, and Th1-derived IFN-γ and TNF-α directly impaired human ang...
journal_title:Cell reports
pub_type: 杂志文章
doi:10.1016/j.celrep.2018.07.019
更新日期:2018-08-07 00:00:00
abstract::CISD2 is located within the chromosome 4q region frequently deleted in hepatocellular carcinoma (HCC). Mice with Cisd2 heterozygous deficiency develop a phenotype similar to the clinical manifestation of nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH). Cisd2 haploinsufficiency causes a...
journal_title:Cell reports
pub_type: 杂志文章
doi:10.1016/j.celrep.2017.10.099
更新日期:2017-11-21 00:00:00
abstract::Proper control of DNA replication is essential to ensure faithful transmission of genetic material and prevent chromosomal aberrations that can drive cancer progression and developmental disorders. DNA replication is regulated primarily at the level of initiation and is under strict cell-cycle regulation. Importantly,...
journal_title:Cell reports
pub_type: 杂志文章
doi:10.1016/j.celrep.2014.10.005
更新日期:2014-11-06 00:00:00
abstract::The cerebral cortex is organized in vertical columns that contain neurons with similar functions. The cellular micro-architecture of such columns is an essential determinant of brain dynamics and cortical information processing. However, a detailed understanding of columns is incomplete, even in the best studied corti...
journal_title:Cell reports
pub_type: 杂志文章
doi:10.1016/j.celrep.2019.04.007
更新日期:2019-04-30 00:00:00
abstract::The germinal center (GC) response is critical for generating high-affinity humoral immunity and immunological memory, which forms the basis of successful immunization. Control of the GC response is thought to require follicular regulatory T (Tfr) cells, a subset of suppressive Foxp3+ regulatory T cells located within ...
journal_title:Cell reports
pub_type: 杂志文章
doi:10.1016/j.celrep.2019.12.076
更新日期:2020-01-21 00:00:00
abstract::Angiogenesis is a highly regulated process essential for organ development and maintenance, and its deregulation contributes to inflammation, cardiac disorders, and cancer. The Ca2+/nuclear factor of activated T cells (NFAT) signaling pathway is central to endothelial cell angiogenic responses, and it is activated by ...
journal_title:Cell reports
pub_type: 杂志文章
doi:10.1016/j.celrep.2018.04.008
更新日期:2018-05-08 00:00:00
abstract::Oct4 is an essential regulator of pluripotency in vivo and in vitro in embryonic stem cells, as well as a key mediator of the reprogramming of somatic cells into induced pluripotent stem cells. It is not known whether activation and/or repression of specific genes by Oct4 is relevant to these functions. Here, we show ...
journal_title:Cell reports
pub_type: 杂志文章
doi:10.1016/j.celrep.2011.12.002
更新日期:2012-02-23 00:00:00
abstract::Cellular differentiation is associated with dynamic chromatin remodeling in establishing a cell-type-specific epigenomic landscape. Here, we find that mouse testis-specific and replication-dependent histone H3 variant H3t is essential for very early stages of spermatogenesis. H3t gene deficiency leads to azoospermia b...
journal_title:Cell reports
pub_type: 杂志文章
doi:10.1016/j.celrep.2016.12.065
更新日期:2017-01-17 00:00:00
abstract::Hepatocyte nuclear factor 4α (HNF4α) is a dimeric transcription factor that controls as much as 60% of all liver genes. However, how it achieves such broad functional diversity is unknown. Here, we show that inflammation and immune pathway genes are differentially regulated in an isoform-dependent manner, confirming t...
journal_title:Cell reports
pub_type: 杂志文章
doi:10.1016/j.celrep.2019.02.033
更新日期:2019-03-05 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::The rate at which genomes diverge during speciation is unknown, as are the physical dynamics of the process. Here, we compare full genome sequences of 32 butterflies, representing five species from a hybridizing Heliconius butterfly community, to examine genome-wide patterns of introgression and infer how divergence e...
journal_title:Cell reports
pub_type: 杂志文章
doi:10.1016/j.celrep.2013.09.042
更新日期:2013-11-14 00:00:00
abstract::It is currently assumed that 3D chromosomal organization plays a central role in transcriptional control. However, depletion of cohesin and CTCF affects the steady-state levels of only a minority of transcripts. Here, we use high-resolution Capture Hi-C to interrogate the dynamics of chromosomal contacts of all annota...
journal_title:Cell reports
pub_type: 杂志文章
doi:10.1016/j.celrep.2020.107929
更新日期:2020-07-21 00:00:00
abstract::Trinucleotide repeat expansions involving CTG/CAG triplets are responsible for several neurodegenerative disorders, including myotonic dystrophy and Huntington's disease. Because expansions trigger the disease, contracting repeat length could be a possible approach to gene therapy for these disorders. Here, we show th...
journal_title:Cell reports
pub_type: 杂志文章
doi:10.1016/j.celrep.2018.01.083
更新日期:2018-02-20 00:00:00
abstract::Presenilin 1 (PS1) is the catalytic core of γ-secretase, which cleaves type 1 transmembrane proteins, including the amyloid precursor protein (APP). PS1 also has γ-secretase-independent functions, and dominant PS1 missense mutations are the most common cause of familial Alzheimer's disease (FAD). Whether PS1 FAD mutat...
journal_title:Cell reports
pub_type: 杂志文章
doi:10.1016/j.celrep.2013.10.018
更新日期:2013-11-27 00:00:00
abstract::Spinal cord longitudinal axons comprise some of the longest axons in our body. However, mechanisms that drive this extra long-distance axonal growth are largely unclear. We found that ascending axons of rapidly adapting (RA) mechanoreceptors closely abut a previously undescribed population of roof plate-derived radial...
journal_title:Cell reports
pub_type: 杂志文章
doi:10.1016/j.celrep.2018.05.025
更新日期:2018-06-05 00:00:00