Abstract:
:Vacuoles are essential organelles in plants, playing crucial roles, such as cellular material degradation, ion and metabolite storage, and turgor maintenance. Vacuoles receive material via the endocytic, secretory, and autophagic pathways. Membrane fusion is the last step during which prevacuolar compartments (PVCs) and autophagosomes fuse with the vacuole membrane (tonoplast) to deliver cargoes. Protein components of the canonical intracellular fusion machinery that are conserved across organisms, including Arabidopsis thaliana, include complexes, such as soluble N-ethylmaleimide-sensitive factor attachment protein receptors (SNAREs), that catalyze membrane fusion, and homotypic fusion and vacuole protein sorting (HOPS), that serve as adaptors which tether cargo vesicles to target membranes for fusion under the regulation of RAB-GTPases. The mechanisms regulating the recruitment and assembly of tethering complexes are not well-understood, especially the role of RABs in this dynamic regulation. Here, we report the identification of the small synthetic molecule Endosidin17 (ES17), which interferes with synthetic, endocytic, and autophagic traffic by impairing the fusion of late endosome compartments with the tonoplast. Multiple independent target identification techniques revealed that ES17 targets the VPS35 subunit of the retromer tethering complex, preventing its normal interaction with the Arabidopsis RAB7 homolog RABG3f. ES17 interference with VPS35-RABG3f interaction prevents the retromer complex to endosome anchoring, resulting in retention of RABG3f. Using multiple approaches, we show that VPS35-RABG3f-GTP interaction is necessary to trigger downstream events like HOPS complex assembly and fusion of late compartments with the tonoplast. Overall, our results support a role for the interaction of RABG3f-VPS35 as a checkpoint in the control of traffic toward the vacuole.
journal_name
Proc Natl Acad Sci U S Aauthors
Rodriguez-Furlan C,Domozych D,Qian W,Enquist PA,Li X,Zhang C,Schenk R,Winbigler HS,Jackson W,Raikhel NV,Hicks GRdoi
10.1073/pnas.1905321116subject
Has Abstractpub_date
2019-10-15 00:00:00pages
21291-21301issue
42eissn
0027-8424issn
1091-6490pii
1905321116journal_volume
116pub_type
杂志文章abstract::We consider many-body problems in classical mechanics where a wide range of time scales limits what can be computed. We apply the method of optimal prediction to obtain equations that are easier to solve numerically. We demonstrate by examples that optimal prediction can reduce the amount of computation needed to obta...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.97.12.6253
更新日期:2000-06-06 00:00:00
abstract::Bordetella pertussis, the causative agent of whooping cough, secretes several toxins implicated in this disease. One of these putative virulence factors is the adenylate cyclase (AC) toxin that elevates intracellular cAMP in eukaryotic cells to cytotoxic levels. This toxin is a bifunctional protein comprising both AC ...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.89.11.4898
更新日期:1992-06-01 00:00:00
abstract::Unlike other predators that use vision as their primary sensory system, bats compute the three-dimensional (3D) position of flying insects from discrete echo snapshots, which raises questions about the strategies they employ to track and intercept erratically moving prey from interrupted sensory information. Here, we ...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.2011719117
更新日期:2020-11-17 00:00:00
abstract::Much discussion has occurred in recent years on whether observed patterns of structure in island bird communities are the result of competitive interactions among species or independent rates of colonization and extinction. Here two patterns of structure are presented for birds on 12 West Indian islands. Each of four ...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.79.5.1563
更新日期:1982-03-01 00:00:00
abstract::Monoclonal antibodies have been obtained that recognize either the A or B chain of human urinary urokinase. These antibodies identify human urokinase-producing cells and the product of urokinase mRNA. Anti-urokinase monoclonal antibodies precipitate an approximately equal to 54,000-dalton protein synthesized in vitro ...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.81.1.110
更新日期:1984-01-01 00:00:00
abstract::The bacterial TATAAT -10 region sequence was the first promoter element to be identified, but how it functions is still not clear. Because the duplex element is melted during initiation, the effects of substitutions were studied in both single-and double-strand contexts. Band-shift results were particularly unexpected...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.161085798
更新日期:2001-07-31 00:00:00
abstract::Nerve growth factor (NGF) serum levels were measured in 49 patients with asthma and/or rhinoconjunctivitis and/or urticaria-angioedema. Clinical and biochemical parameters, such as bronchial reactivity, total and specific serum IgE levels, and circulating eosinophil cationic protein levels, were evaluated in relation ...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.93.20.10955
更新日期:1996-10-01 00:00:00
abstract::Eph receptor tyrosine kinases and their ephrin ligands regulate cell navigation during normal and oncogenic development. Signaling of Ephs is initiated in a multistep process leading to the assembly of higher-order signaling clusters that set off bidirectional signaling in interacting cells. However, the structural an...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.1004148107
更新日期:2010-06-15 00:00:00
abstract::The intestinal mucosa exists in dynamic balance with trillions of luminal microbes. Disruption of the intestinal epithelial barrier, commonly observed in mucosal inflammation and diseases such as inflammatory bowel diseases (IBDs), is often associated with dysbiosis, particularly decreases in species producing short-c...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.1917597117
更新日期:2020-05-26 00:00:00
abstract::Sleep is recognized as a physiological state associated with learning, with studies showing that knowledge acquisition improves with naps. Little work has examined sleep-dependent learning in people with developmental disorders, for whom sleep quality is often impaired. We examined the effect of natural, in-home naps ...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.1811488115
更新日期:2018-11-13 00:00:00
abstract::McKay et al. [(1996) Science 273, 924-930] suggested that carbonate globules in the meteorite ALH84001 contained the fossil remains of Martian microbes. We have characterized a subpopulation of magnetite (Fe(3)O(4)) crystals present in abundance within the Fe-rich rims of these carbonate globules. We find these Martia...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.051500898
更新日期:2001-02-27 00:00:00
abstract::The hammerhead ribozyme, as engineered by J. Haseloff and W. L. Gerlach [(1988) Nature (London) 334, 585-591], is an RNA molecule containing two regions of conserved nucleotides, a double helix, called helix II, which connects the two conserved regions, and flanking arms of variable sequence, which hybridize the riboz...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.89.13.5710
更新日期:1992-07-01 00:00:00
abstract::Recombinant human granulocyte-macrophage colony-stimulating factor (GM-CSF) was found to increase the adherence of purified peripheral blood monocytes to plastic surfaces and to monolayers of human umbilical vein endothelial cells. With plastic surfaces as a model 9-hr culture with GM-CSF was necessary for enhancement...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.86.18.7169
更新日期:1989-09-01 00:00:00
abstract::Bruton tyrosine kinase (EC 2.7.1.112) [Btk, encoded by Btk in mice and BTK in humans (formerly known as atk, BPK, or emb)], which is variously mutated in chromosome X-linked agammaglobulinemia patients and X-linked immunodeficient (xid) mice, has the pleckstrin homology (PH) domain at its amino terminus. The PH domain...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.91.19.9175
更新日期:1994-09-13 00:00:00
abstract::Acquired resistance to androgen receptor (AR)-targeted therapies compels the development of novel treatment strategies for castration-resistant prostate cancer (CRPC). Here, we report a profound effect of endostatin on prostate cancer cells by efficient intracellular trafficking, direct interaction with AR, reduction ...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.1417660112
更新日期:2015-02-03 00:00:00
abstract::Insertion of trocars, needles, and catheters into unintended tissues or tissue compartments results in hundreds of thousands of complications annually. Current methods for blood vessel cannulation or epidural, chest tube, and initial trocar placement often involve the blind pass of a needle through several layers of t...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.0808274106
更新日期:2009-04-07 00:00:00
abstract::Mus poschiavinus x M. musculus hybrids, which had seven metacentric chromosomes derived from the poschiavinus complement, were repeatedly backcrossed to M. musculus and selected for the chromosome carrying the H-2 complex. A line called T1/Klj was established which had one metacentric chromosome. It was shown by linka...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.68.7.1594
更新日期:1971-07-01 00:00:00
abstract::The 2.1-A resolution crystal structure of wild-type green fluorescent protein and comparison of it with the recently determined structure of the Ser-65 --> Thr (S65T) mutant explains the dual wavelength absorption and photoisomerization properties of the wild-type protein. The two absorption maxima are caused by a cha...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.94.6.2306
更新日期:1997-03-18 00:00:00
abstract::The central nervous system both influences and is influenced by the gastrointestinal system. Most research on this gut-brain connection has focused on how ascending signals from the gut and its microbiome alter brain function. Less attention has focused on how descending signals from the central nervous system alter g...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.2002737117
更新日期:2020-06-09 00:00:00
abstract::Harvey and Kirsten murine sarcoma viruses each encode a structurally and functionally related 21-kilodalton protein (p21), which is the transforming protein of each virus. Using probes from the 0.9-kilobase (kb) p21-coding region of each virus (called v-Ha-ras and v-Ki-ras, respectively), we have molecularly cloned fr...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.79.16.4848
更新日期:1982-08-01 00:00:00
abstract::Due to intrinsic aggressiveness and lack of effective therapies, prognosis of pancreatic cancer remains dismal. Because the only molecular targeted drug approved for pancreatic ductal adenocarcinoma is a kinase inhibitor specific to the epidermal growth factor receptor (EGFR), and this receptor collaborates with anoth...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.1313857110
更新日期:2013-09-17 00:00:00
abstract::Chicken ovalbumin upstream promoter-transcription factor (COUP-TF) genes encode transcription factors belonging to the orphan subfamily of the steroid/thyroid hormone receptor superfamily. Two COUP-TF counterparts have been cloned from mouse. In an attempt to study the function of these genes in the developing central...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.91.10.4451
更新日期:1994-05-10 00:00:00
abstract::Interleukin 2 (IL-2) plays a critical role in the growth and differentiation of lymphoid cells. The IL-2 signal is delivered intracellularly by the IL-2 receptor beta chain (IL-2R beta); however, the mechanism by which the signal reaches the nucleus remains unclear. In this study, we demonstrate the rapid activation o...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.89.6.2022
更新日期:1992-03-15 00:00:00
abstract::The live cold-adapted (ca) A/AA/6/60 influenza vaccine is being commercially developed for worldwide use in children and is being used as a model for other live vaccines. Although it has been proven safe and immunogenic, the molecular basis of cold adaptation has never been determined. To identify sequence changes res...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.90.13.6032
更新日期:1993-07-01 00:00:00
abstract::Respiratory syncytial virus (RSV) can cause devastating lower respiratory tract infections in preterm infants or when other serious health problems are present. Immunoprophylaxis with palivizumab (Synagis), a humanized IgG1 mAb, is the current standard of care for preventing RSV infection in at-risk neonates. We have ...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.1402458111
更新日期:2014-04-22 00:00:00
abstract::Nonribosomal peptides and polyketides are a diverse group of natural products with complex chemical structures and enormous pharmaceutical potential. They are synthesized on modular nonribosomal peptide synthetase (NRPS) and polyketide synthase (PKS) enzyme complexes by a conserved thiotemplate mechanism. Here, we rep...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.1401734111
更新日期:2014-06-24 00:00:00
abstract::The highly ordered and reproducible structure of the fungal prion HET-s makes it an excellent model system for studying the inherent properties of prions, self-propagating infectious proteins that have been implicated in a number of fatal diseases. In particular, the HET-s prion-forming domain readily folds into a rel...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.1322933111
更新日期:2014-04-08 00:00:00
abstract::We reported previously that Go-deficient mice develop severe neurological defects that include hyperalgesia, a generalized tremor, lack of coordination, and a turning syndrome somewhat reminiscent of unilateral lesions of the dopaminergic nigro-striatal pathway. By using frozen coronal sections of serially sectioned b...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.051632598
更新日期:2001-03-13 00:00:00
abstract::Addition of acetylcholine to growing cultures of mouse neuroblastoma cells induced a 37-fold increase in the specific activity of acetylcholinesterase (EC 3.1.1.7). Morphological changes, consisting of neurite-extensions, were also observed during the logarithmic phase of growth of cells stimulated with acetylcholine....
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.69.11.3161
更新日期:1972-11-01 00:00:00
abstract::We have isolated and characterized cDNA and genomic clones that specify a Paracentrotus lividus procollagen chain. The cDNAs code for 160 uninterrupted Gly-Xaa-Yaa triplets and a 252-amino acid carboxyl propeptide. Analysis of the deduced amino acid sequences indicated that the sea urchin polypeptide exhibits structur...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.86.23.9303
更新日期:1989-12-01 00:00:00