Abstract:
:Visual transduction in Drosophila is a G protein-coupled phospholipase C-mediated process that leads to depolarization via activation of the transient receptor potential (TRP) calcium channel. Inactivation-no-afterpotential D (INAD) is an adaptor protein containing PDZ domains known to interact with TRP. Immunoprecipitation studies indicate that INAD also binds to eye-specific protein kinase C and the phospholipase C, no-receptor-potential A (NORPA). By overlay assay and site-directed mutagenesis we have defined the essential elements of the NORPA-INAD association and identified three critical residues in the C-terminal tail of NORPA that are required for the interaction. These residues, Phe-Cys-Ala, constitute a novel binding motif distinct from the sequences recognized by the PDZ domain in INAD. To evaluate the functional significance of the INAD-NORPA association in vivo, we generated transgenic flies expressing a modified NORPA, NORPAC1094S, that lacks the INAD interaction. The transgenic animals display a unique electroretinogram phenotype characterized by slow activation and prolonged deactivation. Double mutant analysis suggests a possible inaccessibility of eye-specific protein kinase C to NORPAC1094S, undermining the observed defective deactivation, and that delayed activation may similarly result from NORPAC1094S being unable to localize in close proximity to the TRP channel. We conclude that INAD acts as a scaffold protein that facilitates NORPA-TRP interactions required for gating of the TRP channel in photoreceptor cells.
journal_name
Proc Natl Acad Sci U S Aauthors
Shieh BH,Zhu MY,Lee JK,Kelly IM,Bahiraei Fdoi
10.1073/pnas.94.23.12682subject
Has Abstractpub_date
1997-11-11 00:00:00pages
12682-7issue
23eissn
0027-8424issn
1091-6490journal_volume
94pub_type
杂志文章abstract::Niemann-Pick C1 (NPC1) and NPC2 proteins are indispensable for the export of LDL-derived cholesterol from late endosomes. Mutations in these proteins result in Niemann-Pick type C disease, a lysosomal storage disease. Despite recent reports of the NPC1 structure depicting its overall architecture, the function of its ...
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.1711716114
更新日期:2017-08-22 00:00:00
abstract::Whole-chromosome copy number alterations, also known as aneuploidy, are associated with adverse consequences in most cells and organisms. However, high frequencies of aneuploidy have been reported to occur naturally in the mammalian liver and brain, fueling speculation that aneuploidy provides a selective advantage 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.1415287111
更新日期:2014-09-16 00:00:00
abstract::Current knowledge of the evolution of the postcranial skeleton in the genus Homo is hampered by a geographically and chronologically scattered fossil record. Here we present a complete characterization of the postcranium of the middle Pleistocene paleodeme from the Sima de los Huesos (SH) and its paleobiological impli...
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.1514828112
更新日期:2015-09-15 00:00:00
abstract::Glucose stimulates insulin secretion from β-cells by increasing intracellular Ca(2+). Ca(2+) then binds to synaptotagmin-7 as a major Ca(2+) sensor for exocytosis, triggering secretory granule fusion and insulin secretion. In type-2 diabetes, insulin secretion is impaired; this impairment is ameliorated by glucagon-li...
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.1513004112
更新日期:2015-08-11 00:00:00
abstract::We investigated the structural and functional alterations of active lamellae during initial cell-cell collision and establishment of cell-cell contacts in wounded cultures of nontransformed rat epitheliocytes (IAR-2 line) and their ras-transformed descendants (C4 line). Typically, the leading edges of nontransformed 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.94.3.879
更新日期:1997-02-04 00:00:00
abstract::The release of urine, or micturition, serves a fundamental physiological function and, in many species, is critical for social communication. In mice, the pattern of urine release is modulated by external and internal factors and transmitted to the spinal cord via the pontine micturition center (PMC). Here, we exploit...
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.2018078118
更新日期:2021-01-05 00:00:00
abstract::Protein phosphorylation is a ubiquitous and one of the most effective means of regulating protein activity. Receptor phosphorylation is a key event in signal transduction. The question, therefore, that arises is whether this modulatory mechanism might produce functional changes in a membrane receptor in the absence of...
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.88.22.10213
更新日期:1991-11-15 00:00:00
abstract::Container-shaped molecules provide structured environments that impart geometric bounds on the motions and conformations of smaller molecular occupants. Moreover, they provide "solvation" that is constrained in time and space. When inwardly directed functional groups are present, they can interact chemically with the ...
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.0501731102
更新日期:2005-08-02 00:00:00
abstract::T cell-mediated autoimmune diseases such as type 1 diabetes (T1D) are believed to be the result in part of inefficient negative selection of self-specific thymocytes. However, the events regulating thymic negative selection are not fully understood. In the current study, we demonstrate that nonobese diabetic (NOD) mic...
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.0900683106
更新日期:2009-03-24 00:00:00
abstract::Synthetic bradykinin, a nonapeptide formed from alpha-2 globulin in plasma, injected intra-arterially or intraperitoneally in cats in doses of 10-50 mug, evoked activity in the central nervous system in pathways associated with the signaling of pain. Similar injections of bradykinin in intact normal cats and dogs evok...
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.63.3.705
更新日期:1969-07-01 00:00:00
abstract::The bacterial hibernating 100S ribosome is a poorly understood form of the dimeric 70S particle that has been linked to pathogenesis, translational repression, starvation responses, and ribosome turnover. In the opportunistic pathogen Staphylococcus aureus and most other bacteria, hibernation-promoting factor (HPF) ho...
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.1709588114
更新日期:2017-09-26 00:00:00
abstract::Chronic, relapsing myelitis has been induced in golden Syrian hamsters by the intracerebral inoculation of measles virus when the animals were less than 1 day old. No acute illness was seen in animals that developed myelitis, and the onset of the myelitis was at 5 to 50 weeks after infection. In most animals the illne...
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.77.7.4297
更新日期:1980-07-01 00:00:00
abstract::Nitrogen metabolism in bacteria and archaea is regulated by a ubiquitous class of proteins belonging to the P(II)family. P(II) proteins act as sensors of cellular nitrogen, carbon, and energy levels, and they control the activities of a wide range of target proteins by protein-protein interaction. The sensing mechanis...
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.1108038108
更新日期:2011-11-22 00:00:00
abstract::Infectious diseases of domesticated animals impact human well-being via food insecurity, loss of livelihoods, and human infections. While much research has focused on parasites that infect single host species, most parasites of domesticated mammals infect multiple species. The impact of multihost parasites varies acro...
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.1817323116
更新日期:2019-04-16 00:00:00
abstract::During the analysis of liver protein expression in the offspring of male mice irradiated with fission-spectrum neutrons, one offspring displayed a heritable 50% decrease in the abundance of two proteins. Homozygous mice lacking detectable quantities of these proteins were obtained through breeding. Characterization of...
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.91.24.11338
更新日期:1994-11-22 00:00:00
abstract::This investigation was undertaken to determine the possible role of growth hormone (GH) in the hormonal regulation of hepatic low density lipoprotein (LDL) receptor expression. Treatment of normal rats with estrogen (ethynylestradiol, 5 mg/kg per day) increased the number of hepatic LDL receptors, and the LDL receptor...
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.89.15.6983
更新日期:1992-08-01 00:00:00
abstract::The human pathogen Mycobacterium tuberculosis encodes a proteasome that carries out regulated degradation of bacterial proteins. It has been proposed that the proteasome contributes to nitrogen metabolism in M. tuberculosis, although this hypothesis had not been tested. Upon assessing M. tuberculosis growth in several...
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.1819468116
更新日期:2019-02-19 00:00:00
abstract::Although the first observations of the inhibitory effect of methylation on gene activity were made almost a decade ago, the mechanism by which methyl groups affect transcription is still obscure. Here we use engineered promoters methylated in vitro in transient transfections to study the mechanism by which methylation...
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.89.21.10119
更新日期:1992-11-01 00:00:00
abstract::We have isolated rat brain cDNA clones encoding AE2, a homologue of the erythrocyte anion exchanger, band 3 (AE1). Immunocytochemistry and in situ hybridization reveal that, in brain, AE2 expression is restricted to the basolateral membrane of the choroid plexus epithelium. Expression of a full-length mouse AE2 cDNA i...
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.87.14.5278
更新日期:1990-07-01 00:00:00
abstract::The four-helical bundle soluble N-ethylmaleimide-sensitive fusion protein (NSF) attachment protein receptor (SNARE) complex that mediates intracellular membrane fusion events contains a highly conserved ionic layer at the center of an otherwise hydrophobic core. This layer has an undetermined function; it consists of ...
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.251547598
更新日期:2001-12-04 00:00:00
abstract::Herpesviruses require a nuclear egress complex (NEC) for efficient transit of nucleocapsids from the nucleus to the cytoplasm. The NEC orchestrates multiple steps during herpesvirus nuclear egress, including disruption of nuclear lamina and particle budding through the inner nuclear membrane. In the important human pa...
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.1511140112
更新日期:2015-07-21 00:00:00
abstract::Previous work has shown that serotonin induces an increase in membrane K+ conductance in Aplysia neuron R15 and that this response is mediated by cAMP. The present study examines the role of protein phosphorylation in the response to serotonin. A specific inhibitor of cAMP-dependent protein kinase was injected intrace...
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.79.12.3877
更新日期:1982-06-01 00:00:00
abstract::Immediate postretrieval bilateral blockade of long-acting voltage-dependent calcium channels (L-VDCCs), but not of glutamatergic NMDA receptors, in the dorsal CA1 region of the hippocampus hinders retention of long-term spatial memory in the Morris water maze. Immediate postretrieval bilateral inhibition of calcium/ca...
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.1302356110
更新日期:2013-04-16 00:00:00
abstract::Insight regarding how diverse enzymatic functions and reactions have evolved from ancestral scaffolds is fundamental to understanding chemical and evolutionary biology, and for the exploitation of enzymes for biotechnology. We undertook an extensive computational analysis using a unique and comprehensive combination 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.1706849114
更新日期:2017-11-07 00:00:00
abstract::Intrinsically photosensitive retinal ganglion cells (ipRGCs) expressing the photopigment melanopsin (OPN4), together with rods and cones, provide light information driving nonvisual light responses. We examined nonvisual photoreception in mice lacking RPE65, a protein that is required for regeneration of visual chromo...
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.0600934103
更新日期:2006-07-05 00:00:00
abstract::The Ly-6 locus encodes several cell surface proteins whose functions are unknown. Although it is hypothesized that these proteins may be receptors, there is no direct evidence that they bind a ligand. Herein we present evidence that Ly-6A.2, a Ly-6 protein expressed on T lymphocytes, binds a ligand expressed on normal...
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.92.10.4294
更新日期:1995-05-09 00:00:00
abstract::Better understanding myelination of peripheral nerves would benefit patients affected by peripheral neuropathies, including Charcot-Marie-Tooth disease. Little is known about the role the Golgi compartment plays in Schwann cell (SC) functions. Here, we studied the role of Golgi in myelination of peripheral nerves in m...
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.2007432117
更新日期:2020-11-10 00:00:00
abstract::Creatine kinase from rabbit muscle has been specifically labeled with a derivative of a nitroxide free radical on the two essential sulfhydryl groups, one per active site. The conformation in the environment of the enzyme-bound free radical and the change in conformation induced upon binding of the substrate, metal ad...
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.64.1.219
更新日期:1969-09-01 00:00:00
abstract::Human transcription factor IIA (TFIIA) is composed of three subunits (alpha, beta, and gamma). TFIIA interacts with the TATA-box binding protein and can overcome repression of transcription. TFIIA was found to be necessary for VP16-mediated transcriptional activation through a coactivator function. We have separated 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.93.13.6583
更新日期:1996-06-25 00:00:00
abstract::A procedure is described for selection of temperature-sensitive mutants affecting fatty-acid synthesis based upon radiation suicide of wild-type organisms by tritiated acetate selectively incorporated into fatty acids. At 37 degrees , two of the mutants extensively incorporate fatty-acid supplements provided in the me...
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.69.11.3105
更新日期:1972-11-01 00:00:00