Abstract:
:Many cellular cargoes move bidirectionally along microtubules, driven by teams of plus- and minus-end-directed motor proteins. To probe the forces exerted on cargoes during intracellular transport, we examined latex beads phagocytosed into living mammalian macrophages. These latex bead compartments (LBCs) are encased in membrane and transported along the cytoskeleton by a complement of endogenous kinesin-1, kinesin-2, and dynein motors. The size and refractive index of LBCs makes them well-suited for manipulation with an optical trap. We developed methods that provide in situ calibration of the optical trap in the complex cellular environment, taking into account any variations among cargoes and local viscoelastic properties of the cytoplasm. We found that centrally and peripherally directed forces exerted on LBCs are of similar magnitude, with maximum forces of ~20 pN. During force events greater than 10 pN, we often observe 8-nm steps in both directions, indicating that the stepping of multiple motors is correlated. These observations suggest bidirectional transport of LBCs is driven by opposing teams of stably bound motors that operate near force balance.
journal_name
Proc Natl Acad Sci U S Aauthors
Hendricks AG,Holzbaur EL,Goldman YEdoi
10.1073/pnas.1215462109subject
Has Abstractpub_date
2012-11-06 00:00:00pages
18447-52issue
45eissn
0027-8424issn
1091-6490pii
1215462109journal_volume
109pub_type
杂志文章abstract::We demonstrate that poly(dA-dT) can adopt two conformations in solution, with the relative proportions dependent on the nature and concentration of the counter ion and cationic ligands. The synthetic DNA exhibits a dinucleotide repeat conformation on addition of CsF and Me4NCl at molar concentrations, with the NMR spe...
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.78.7.4063
更新日期:1981-07-01 00:00:00
abstract::The levels of c-myc, c-fos, and JE mRNAs accumulate in a biphasic pattern following infection of quiescent BALB/c 3T3 mouse cells with polyomavirus. Maximal levels of c-myc and c-fos mRNAs were seen within 1 hr and were nearly undetectable at 6 hr after infection. At 12 hr after infection mRNA levels were again maxima...
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.84.5.1210
更新日期:1987-03-01 00:00:00
abstract::Three components of differentiated muscle membrane, the acetylcholine receptor, acetylcholinesterase (EC 3.1.1.7; acetylcholine hydrolase), and adenylate cyclase [EC 4.6.1.1; ATP pyrophosphate-lyase (cyclizing)], appear simultaneously during myogenesis in cultures of embryonic chick muscle, after the main period of ra...
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.71.8.3208
更新日期:1974-08-01 00:00:00
abstract::Aminoacyl-tRNAs are generally formed by direct attachment of an amino acid to tRNAs by aminoacyl-tRNA synthetases, but Gln-tRNA is an exception to this rule. Gln-tRNA(Gln) is formed by this direct pathway in the eukaryotic cytosol and in protists or fungi mitochondria but is formed by an indirect transamidation pathwa...
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.0712299105
更新日期:2008-04-29 00:00:00
abstract::The replication initiator proteins encoded by the pT181 and related plasmids have sequence-specific DNA binding and topoisomerase activities. These proteins create a site-specific nick in one strand of the DNA at the origin of replication that serves as a primer for the initiation of replication. To define the regions...
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.89.7.3083
更新日期:1992-04-01 00:00:00
abstract::Discrete growing spiral modes are calculated, on the basis of principles of stellar dynamics, according to the recently developed asymptotic theory of density waves for spiral structure in galaxies. From the growth rates obtained, it appears likely that several spiral modes coexist in a given disk galaxy. General prop...
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.74.11.4726
更新日期:1977-11-01 00:00:00
abstract::αβ T-cell repertoire selection is mediated by peptide-MHC complexes presented by thymic epithelial or myeloid cells, and by lipid-CD1 complexes expressed by thymocytes. γδ T-cell repertoire selection, by contrast, is largely unresolved. Mice mutant for Skint-1, a unique Ig superfamily gene, do not develop canonical Vγ...
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.1010890108
更新日期:2011-02-22 00:00:00
abstract::J-domain chaperones are involved in the efficient handover of misfolded/partially folded proteins to Hsp70 but also function independently to protect against cell death. Due to their high flexibility, the mechanism by which they regulate the Hsp70 cycle and how specific substrate recognition is performed remains unkno...
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.1914999116
更新日期:2019-10-22 00:00:00
abstract::Using T- and B-cell deficient C.B-17 mice with the scid mutation, we have previously documented the existence of a T-cell-independent but interferon gamma-dependent pathway of macrophage activation that confers upon the host partial resistance to the facultative intracellular bacterium Listeria monocytogenes. This pat...
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.89.3.1011
更新日期:1992-02-01 00:00:00
abstract::The mechanism of phospholipase C regulation by inhibitory receptors was analyzed both in intact and in permeabilized rat thyroid cells (FRTL5). In this system, the muscarinic agonist carbachol inhibited phospholipase C, as indicated by the decrease in the basal levels of inositol 1,4,5-trisphosphate as well as by the ...
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.87.12.4889
更新日期:1990-06-01 00:00:00
abstract::Gradients of extracellular signaling molecules and transcription factors are used in a variety of developmental processes, including the patterning of the Drosophila embryo, the establishment of diverse neuronal cell types in the vertebrate neural tube, and the anterior-posterior patterning of vertebrate limbs. Here, ...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章,评审
doi:10.1073/pnas.0806476105
更新日期:2008-12-23 00:00:00
abstract::Several mouse models have already proved valuable for investigating hypertrophic responses to cardiac stress. Here, we characterize one caused by a well defined single copy transgene, RenTgMK, that genetically clamps plasma renin and thence angiotensin II at high levels. All of the transgenic males develop concentric ...
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.0307333101
更新日期:2004-03-02 00:00:00
abstract::Ubiquitin C-terminal hydrolase L1 (UCH-L1) is one of the most abundant and enigmatic enzymes of the CNS. Based on existing UCH-L1 knockout models, UCH-L1 is thought to be required for the maintenance of axonal integrity, but not for neuronal development despite its high expression in neurons. Several lines of evidence...
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.1812413116
更新日期:2019-04-16 00:00:00
abstract::Taking advantage of a fluorescent Ca(2+) indicator selectively targeted to the trans-Golgi lumen, we here demonstrate that its Ca(2+) homeostatic mechanisms are distinct from those of the other Golgi subcompartments: (i) Ca(2+) uptake depends exclusively on the activity of the secretory pathway Ca(2+) ATPase1 (SPCA1),...
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.1004702107
更新日期:2010-05-18 00:00:00
abstract::Experiments were designed to determine the interrelationship between cyclic AMP and Ca(2+) during the processes of sperm capacitation and the acrosome reaction. In minimal culture media containing pyruvate and lactate as substrates, guinea pig spermatozoa required a minimum of 1.0-1.5 hr to capacitate in the presence ...
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.76.11.5699
更新日期:1979-11-01 00:00:00
abstract::The density of benzodiazepine/gamma-aminobutyric acid receptor binding sites was lower in the midbrain of seizure-susceptible gerbils compared to control seizure-resistant gerbils. Binding of [3H]diazepam to high-affinity brain-specific sites in membrane homogenates of gerbil brain showed a 20-30% lower binding in mid...
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.82.19.6701
更新日期:1985-10-01 00:00:00
abstract::Although it is known that the c-myc oncogene is rearranged in a head-to-head fashion with the immunoglobulin heavy chain locus in mouse plasmacytomas, it has not been clear whether the c-myc oncogene is translocated to the heavy chain locus on mouse chromosome 12 or whether the heavy chain locus is translocated to the...
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.82.12.4212
更新日期:1985-06-01 00:00:00
abstract::Human T-lymphotropic virus type 1 (HTLV-1) is a retrovirus that causes malignant and inflammatory diseases in ∼10% of infected people. A typical host has between 10(4) and 10(5) clones of HTLV-1-infected T lymphocytes, each clone distinguished by the genomic integration site of the single-copy HTLV-1 provirus. The HTL...
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.1423199113
更新日期:2016-03-15 00:00:00
abstract::It is widely accepted that modern humans originated in sub-Saharan Africa approximately 150-200 thousand years ago (ka), but their route of dispersal across the currently hyperarid Sahara remains controversial. Given that the first modern humans north of the Sahara are found in the Levant approximately 120-90 ka, nort...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 历史文章,杂志文章
doi:10.1073/pnas.0804472105
更新日期:2008-10-28 00:00:00
abstract::The deadly symptoms of malaria occur as Plasmodium parasites replicate within blood cells. Members of several variant surface protein families are expressed on infected blood cell surfaces. Of these, the largest and most ubiquitous are the Plasmodium-interspersed repeat (PIR) proteins, with more than 1,000 variants in...
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.2016775117
更新日期:2020-12-15 00:00:00
abstract::Coral bleaching, caused by heat stress, is accompanied by the light-induced loss of photosynthetic pigments in in situ symbiotic dinoflagellate algae (Symbiodinium spp.). However, the molecular mechanisms responsible for pigment loss are poorly understood. Here, we show that moderate heat stress causes photobleaching ...
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.0708554105
更新日期:2008-03-18 00:00:00
abstract::Alu elements are a family of interspersed repeats that have mobilized throughout primate genomes by retroposition from a few "master" genes. Among the 500,000 Alu elements in the human genome are members of the human-specific subfamily that are not fixed in the human species; that is, not all chromosomes carry an Alu ...
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.91.25.12288
更新日期:1994-12-06 00:00:00
abstract::We establish size limitations for assembling structures of controlled size and shape out of colloidal particles with short-ranged interactions. Through simulations we show that structures with highly variable shapes made out of dozens of particles can form with high yield, as long as each particle in the structure bin...
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.1411765111
更新日期:2014-11-11 00:00:00
abstract::Recent genome-wide nucleosome mappings along with bioinformatics studies have confirmed that the DNA sequence plays a more important role in the collective organization of nucleosomes in vivo than previously thought. Yet in living cells, this organization also results from the action of various external factors like D...
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.0909511106
更新日期:2009-12-29 00:00:00
abstract::The tubercle bacillus parasitizes macrophages by inhibiting phagosome maturation into the phagolysosome. This phenomenon underlies the tuberculosis pandemic involving 2 billion people. We report here how Mycobacterium tuberculosis causes phagosome maturation arrest. A glycosylated M. tuberculosis phosphatidylinositol ...
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.0737613100
更新日期:2003-04-29 00:00:00
abstract::Pair-bond formation depends vitally on neuromodulatory signaling within the nucleus accumbens, but the neuronal dynamics underlying this behavior remain unclear. Using 1-photon in vivo Ca2+ imaging in monogamous prairie voles, we found that pair bonding does not elicit differences in overall nucleus accumbens Ca2+ act...
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.1917287117
更新日期:2020-05-19 00:00:00
abstract::An in-depth knowledge of the interaction of water with amorphous silica is critical to fundamental studies of interfacial hydration water, as well as to industrial processes such as catalysis, nanofabrication, and chromatography. Silica has a tunable surface comprising hydrophilic silanol groups and moderately hydroph...
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.1722263115
更新日期:2018-03-20 00:00:00
abstract::The TFIID transcription initiation complex is composed of TBP and multiple TAFs. Studies in unicellular systems indicate that TAF250 is required for progression through G(1)/S of the cell cycle and repression of apoptosis. Here we extend these in vivo studies by determining the developmental requirements for TAF250 in...
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.97.3.1154
更新日期:2000-02-01 00:00:00
abstract::Natural killer (NK) cells provide in vivo control of orthopoxvirus infections in association with their expansion in the draining lymph node (LN), where they are normally very rare. The mechanism of this expansion is unclear. Herein, we determined that NK-cell depletion results in enhanced infection following footpad ...
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.1220456110
更新日期:2013-01-02 00:00:00
abstract::Chronic psychosocial stress/trauma represents an increasing burden in our modern society and a risk factor for the development of mental disorders, including posttraumatic stress disorder (PTSD). PTSD, in turn, is highly comorbid with a plethora of inflammatory disorders and has been associated with increased bone fra...
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.1819218116
更新日期:2019-04-23 00:00:00