PINCH in the Cellular Stress Response to Tau-Hyperphosphorylation
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{"title"=>"PINCH in the Cellular Stress Response to Tau-Hyperphosphorylation", "type"=>"journal", "authors"=>[{"first_name"=>"Ahmet Yunus", "last_name"=>"Ozdemir", "scopus_author_id"=>"55890180600"}, {"first_name"=>"Inna", "last_name"=>"Rom", "scopus_author_id"=>"26538755200"}, {"first_name"=>"Jane", "last_name"=>"Kovalevich", "scopus_author_id"=>"36863818500"}, {"first_name"=>"William", "last_name"=>"Yen", "scopus_author_id"=>"35082969000"}, {"first_name"=>"Radhika", "last_name"=>"Adiga", "scopus_author_id"=>"55620375900"}, {"first_name"=>"Rajnish S.", "last_name"=>"Dave", "scopus_author_id"=>"8743437800"}, {"first_name"=>"Dianne", "last_name"=>"Langford", "scopus_author_id"=>"7005059205"}], "year"=>2013, "source"=>"PLoS ONE", "identifiers"=>{"isbn"=>"1932-6203 (Electronic)\\r1932-6203 (Linking)", "pmid"=>"23554879", "doi"=>"10.1371/journal.pone.0058232", "pui"=>"368517981", "issn"=>"19326203", "sgr"=>"84874896727", "scopus"=>"2-s2.0-84874896727"}, "id"=>"43b9ce12-0f77-33a4-8b74-e5d525bcc3ff", "abstract"=>"Particularly interesting new cysteine- histidine- rich protein (PINCH) is an adaptor protein that our data have shown is required for neurite extension under stressful conditions. Our previous studies also report that PINCH is recalled by neurons showing decreased levels of synaptodendritic signaling proteins such as MAP2 or synaptophysin in the brains of human immunodeficiency virus (HIV) patients. The current study addressed potential role(s) for PINCH in neurodegenerative diseases. Mass spectrometry predicted the interaction of PINCH with Tau and with members of the heat shock response. Our in vitro data confirmed that PINCH binds to hyperphosphorylated (hp) Tau and to E3 ubiquitin ligase, carboxy-terminus of heat shock-70 interacting protein. Silencing PINCH prior to induction of hp-Tau resulted in more efficient clearance of accumulating hp-Tau, suggesting that PINCH may play a role in stabilizing hp-Tau. Accumulation of hp-Tau is implicated in more than 20 neuropathological diseases including Alzheimer's disease (AD), frontotemporal dementia (FTD), and human immunodeficiency virus encephalitis (HIVE). Analyses of brain tissues from HIVE, AD and FTD patients showed that PINCH is increased and binds to hp-Tau. These studies address a new mechanism by which AD and HIV may intersect and identify PINCH as a contributing factor to the accumulation of hyperphosphorylated Tau.", "link"=>"http://www.mendeley.com/research/pinch-cellular-stress-response-tauhyperphosphorylation", "reader_count"=>15, "reader_count_by_academic_status"=>{"Unspecified"=>1, "Professor > Associate Professor"=>1, "Student > Doctoral Student"=>2, "Researcher"=>2, "Student > Ph. D. Student"=>4, "Student > Master"=>4, "Other"=>1}, "reader_count_by_user_role"=>{"Unspecified"=>1, "Professor > Associate Professor"=>1, "Student > Doctoral Student"=>2, "Researcher"=>2, "Student > Ph. D. Student"=>4, "Student > Master"=>4, "Other"=>1}, "reader_count_by_subject_area"=>{"Unspecified"=>1, "Biochemistry, Genetics and Molecular Biology"=>1, "Mathematics"=>1, "Agricultural and Biological Sciences"=>3, "Medicine and Dentistry"=>4, "Neuroscience"=>2, "Design"=>1, "Social Sciences"=>1, "Computer Science"=>1}, "reader_count_by_subdiscipline"=>{"Design"=>{"Design"=>1}, "Medicine and Dentistry"=>{"Medicine and Dentistry"=>4}, "Neuroscience"=>{"Neuroscience"=>2}, "Social Sciences"=>{"Social Sciences"=>1}, "Agricultural and Biological Sciences"=>{"Agricultural and Biological Sciences"=>3}, "Computer Science"=>{"Computer Science"=>1}, "Biochemistry, Genetics and Molecular Biology"=>{"Biochemistry, Genetics and Molecular Biology"=>1}, "Mathematics"=>{"Mathematics"=>1}, "Unspecified"=>{"Unspecified"=>1}}, "reader_count_by_country"=>{"Germany"=>1, "Russia"=>1}, "group_count"=>0}

Scopus | Further Information

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Figshare

  • {"files"=>["https://ndownloader.figshare.com/files/1012298"], "description"=>"<p>shRNA sequence data for human PINCH1 and 2.</p>", "links"=>[], "tags"=>["pinch1"], "article_id"=>672704, "categories"=>["Neuroscience", "Mental Health", "Infectious Diseases", "Molecular Biology", "Cell Biology"], "users"=>["Ahmet Yunus Ozdemir", "Inna Rom", "Jane Kovalevich", "William Yen", "Radhika Adiga", "Rajnish S. Dave", "Dianne Langford"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0058232.t001", "stats"=>{"downloads"=>2, "page_views"=>4, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_shRNA_sequence_data_for_human_PINCH1_and_2_/672704", "title"=>"shRNA sequence data for human PINCH1 and 2.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2013-03-12 00:45:04"}
  • {"files"=>["https://ndownloader.figshare.com/files/985060"], "description"=>"<p>A) Representative Western blot showing levels of PINCH1, hpTau, total Tau, Hsp90, Hsp70 and CHIP from neurons grown in media without PBMCs (con), neurons exposed to supernatant from control PBMCs without HIV infection (PBMC), supernatant from PBMCs infected with HIV (PBMC+HIV), or neurons exposed to cell-free virus (HIV). Grb-2 was used as the loading control. B) Fold change in hpTau/Total Tau.</p>", "links"=>[], "tags"=>["neurons", "supernatant", "hiv-infected", "pbmcs", "hp-tau"], "article_id"=>650523, "categories"=>["Neuroscience", "Mental Health", "Infectious Diseases", "Molecular Biology", "Cell Biology"], "users"=>["Ahmet Yunus Ozdemir", "Inna Rom", "Jane Kovalevich", "William Yen", "Radhika Adiga", "Rajnish S. Dave", "Dianne Langford"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0058232.g002", "stats"=>{"downloads"=>0, "page_views"=>19, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Exposure_of_neurons_to_supernatant_from_HIV_infected_PBMCs_results_in_increased_PINCH_hp_Tau_and_CHIP_/650523", "title"=>"Exposure of neurons to supernatant from HIV-infected PBMCs results in increased PINCH, hp-Tau and CHIP.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-03-13 09:27:40"}
  • {"files"=>["https://ndownloader.figshare.com/files/985058"], "description"=>"<p>Representative Western blot of A) neurons exposed to TNF-α; B) graphic representation of fold change of PINCH1, hp-Tau, total Tau and CHIP levels in TNF-α treated neurons over control. Results are from 4 separate experiments and are expressed as fold change over control. * p<0.005, **p<0.001 by one-way ANOVA with Tukey-Kramer post-hoc analyses. Grb-2 was used as the loading control. C) Fold change in hp-Tau/Total Tau * p = 0.0293 by one-tailed paired T-test.</p>", "links"=>[], "tags"=>["neurons", "hp-tau"], "article_id"=>650522, "categories"=>["Neuroscience", "Mental Health", "Infectious Diseases", "Molecular Biology", "Cell Biology"], "users"=>["Ahmet Yunus Ozdemir", "Inna Rom", "Jane Kovalevich", "William Yen", "Radhika Adiga", "Rajnish S. Dave", "Dianne Langford"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0058232.g001", "stats"=>{"downloads"=>0, "page_views"=>17, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Exposure_of_neurons_to_TNF_945_results_in_increased_levels_of_PINCH_hp_Tau_and_CHIP_/650522", "title"=>"Exposure of neurons to TNF-α results in increased levels of PINCH, hp-Tau and CHIP.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-03-13 09:27:31"}
  • {"files"=>["https://ndownloader.figshare.com/files/985071"], "description"=>"<p>A) Western analyses of anterior frontal cortex (Ant-Fc), ventro-lateral posterior cortex (V-L-post-FC), posterior frontal cortex (post-FC), cerebellum (CB). B) Double immunofluorescence labeling of PINCH (green) and hp-Tau (red), co-localization (yellow) in hippocampal tissue from a wild-type mouse and the Tau-Tg mouse and respectively.</p>", "links"=>[], "tags"=>["hp-tau", "pinch", "tau", "transgenic"], "article_id"=>650531, "categories"=>["Neuroscience", "Mental Health", "Infectious Diseases", "Molecular Biology", "Cell Biology"], "users"=>["Ahmet Yunus Ozdemir", "Inna Rom", "Jane Kovalevich", "William Yen", "Radhika Adiga", "Rajnish S. Dave", "Dianne Langford"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0058232.g007", "stats"=>{"downloads"=>4, "page_views"=>36, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Expression_levels_of_hp_Tau_and_PINCH_in_brain_tissue_from_human_Tau_transgenic_mouse_/650531", "title"=>"Expression levels of hp-Tau and PINCH in brain tissue from human Tau transgenic mouse.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-03-13 09:28:30"}
  • {"files"=>["https://ndownloader.figshare.com/files/985063"], "description"=>"<p>A) LIMS-specific deletion mutations predict that LIM1 and 2 domains of PINCH1 bind to hp-Tau. Expression plasmids for mutants (ΔLIMS 1–5) and full-length PINCH each with a FLAG-tag were generated via a PCR based strategy. Neuronal lysates were immunoprecipitated with anti-FLAG antibody and reacted with A) anti-hp-Tau (AT8), B) Nck-2 or E) MAP2 antibodies. Arrows indicate immunoreactive bands. FL, full length; ΔLIM, delta LIM indicates the LIM domain that was deleted; FLAG, epitope N-DYKDDDDK-C tag; Nck2, cytoplasmic adaptor protein that interacts with PINCH LIM4; MAP2, microtubule associated protein-2.</p>", "links"=>[], "tags"=>["interacts", "lim", "domains"], "article_id"=>650525, "categories"=>["Neuroscience", "Mental Health", "Infectious Diseases", "Molecular Biology", "Cell Biology"], "users"=>["Ahmet Yunus Ozdemir", "Inna Rom", "Jane Kovalevich", "William Yen", "Radhika Adiga", "Rajnish S. Dave", "Dianne Langford"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0058232.g004", "stats"=>{"downloads"=>0, "page_views"=>13, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_hp_Tau_interacts_with_the_first_and_second_LIM_domains_of_PINCH_/650525", "title"=>"hp-Tau interacts with the first and second LIM domains of PINCH.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-03-13 09:27:49"}
  • {"files"=>["https://ndownloader.figshare.com/files/985061"], "description"=>"<p>Neuronal lysate was immunoprecipitated with anti PINCH and reacted with antibodies against hp-Tau A) AT100 and B) AT8. C) Neuronal lysate was immunoprecipitated with anti-AT8 antibody and reacted with anti-PINCH, anti-Hsp90, anti-Hsp70 and CHIP. D) Neuronal lysate was immunoprecipitated with anti-PINCH antibody and reacted with anti-Hsp90, anti-Hsp70, anti-CHIP and anti-ILK. E) Reciprocal IP with anti-CHIP and reaction with anti-PINCH. F) Neuronal lysate was treated with (+) or without (−) phosphatase and immunoprecipitated with anti-HT7 antibody against total Tau and reacted with anti-PINCH antibody. G) The same neuronal lysate with (+) and without (−) phosphatase was immunoblotted with anti-HT7 and anti-PINCH antibodies without immunoprecipitation. Arrows indicate immunoreactive bands. Hc, heavy chain; lc, light chain; No IP (lysate), beads only (IgG); immunoprecipitation (IP).</p>", "links"=>[], "tags"=>["immunoprecipitations", "pinch", "interacts", "hp-tau"], "article_id"=>650524, "categories"=>["Neuroscience", "Mental Health", "Infectious Diseases", "Molecular Biology", "Cell Biology"], "users"=>["Ahmet Yunus Ozdemir", "Inna Rom", "Jane Kovalevich", "William Yen", "Radhika Adiga", "Rajnish S. Dave", "Dianne Langford"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0058232.g003", "stats"=>{"downloads"=>2, "page_views"=>131, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Reciprocal_immunoprecipitations_indicate_PINCH_interacts_with_hp_Tau_and_CHIP_/650524", "title"=>"Reciprocal immunoprecipitations indicate PINCH interacts with hp-Tau and CHIP.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-03-13 09:27:46"}
  • {"files"=>["https://ndownloader.figshare.com/files/985073"], "description"=>"<p>The proteins from frontal cortex homogenates from normal, different Braak stages (1, 3, 5) of Alzheimer's disease (AD), HIV encephalitis (HIVE), and frontotemporal dementia (FTD) patients were fractionated into RAB (most soluble, RB), RIPA (less soluble, RB) and formic acid (FA) (least soluble). Representative Western blots from A) normal control, AD, HIVE, and FTD showing levels of PINCH, hpTau (s396) and total Tau (HT7). B) Coomassie stained gel of the same cases indicating total protein in each fraction. Compared to the control, increased levels of hp-Tau and PINCH are observed in disease cases. Loss of Tau and PINCH solubility are apparent in AD, HIVE and FTD, as well. Arrow in the FTD case indicates a blank lane in the gel.</p>", "links"=>[], "tags"=>["tau"], "article_id"=>650533, "categories"=>["Neuroscience", "Mental Health", "Infectious Diseases", "Molecular Biology", "Cell Biology"], "users"=>["Ahmet Yunus Ozdemir", "Inna Rom", "Jane Kovalevich", "William Yen", "Radhika Adiga", "Rajnish S. Dave", "Dianne Langford"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0058232.g008", "stats"=>{"downloads"=>1, "page_views"=>6, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_PINCH_levels_in_relation_to_changes_in_Tau_solubility_/650533", "title"=>"PINCH levels in relation to changes in Tau solubility.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-03-13 09:28:39"}
  • {"files"=>["https://ndownloader.figshare.com/files/1012316"], "description"=>"<p>PINCH deletion mutants and sequences.</p>", "links"=>[], "tags"=>["deletion", "mutants"], "article_id"=>672726, "categories"=>["Neuroscience", "Mental Health", "Infectious Diseases", "Molecular Biology", "Cell Biology"], "users"=>["Ahmet Yunus Ozdemir", "Inna Rom", "Jane Kovalevich", "William Yen", "Radhika Adiga", "Rajnish S. Dave", "Dianne Langford"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0058232.t002", "stats"=>{"downloads"=>3, "page_views"=>6, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_PINCH_deletion_mutants_and_sequences_/672726", "title"=>"PINCH deletion mutants and sequences.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2013-03-12 00:45:26"}
  • {"files"=>["https://ndownloader.figshare.com/files/985069"], "description"=>"<p>A) Representative Western blot showing PINCH, soluble hp-Tau (s262) and total Tau (HT7) in age-matched controls (normal), AD Braak stages 1, 3, 5 (Br1, 3, 5), and HIV encephalitis (HIVE) patients. B) Graphic representation of percent total Tau that is hyperphosphorylated (hpTau/total Tau) in each case compared to control. C-G) Double immunofluorescence labeling of a frontal cortex tissue from a representative AD patient (Braak stage 3). C) from top left, panel shows DAPI for nuclei in blue; top right, PINCH in green; lower left, hp-Tau (s396) in red; lower right, co-localization of PINCH and hp-Tau. Arrowheads, arrows and asterisks indicate the same area in the tissue section. D) Double-immunolabeling of PINCH (green) and hp-Tau (red), co-localization, yellow; E) PINCH (green) and CHIP (red), co-localization (yellow); F) PINCH (green) and Hsp70 (red), co-localization (yellow); G) PINCH (green) and Hsp90 (red), no co-localization; H) Brain homogenate from a representative AD patient (Braak stage 3) immunoprecipitated with anti-PINCH antibody and reacted with anti-hp-Tau (AT8) antibody. Arrows, arrowheads show immunoreactive bands indicating PINCH-hp-Tau interaction.</p>", "links"=>[], "tags"=>["hp-tau", "pinch", "frontal", "cortex"], "article_id"=>650529, "categories"=>["Neuroscience", "Mental Health", "Infectious Diseases", "Molecular Biology", "Cell Biology"], "users"=>["Ahmet Yunus Ozdemir", "Inna Rom", "Jane Kovalevich", "William Yen", "Radhika Adiga", "Rajnish S. Dave", "Dianne Langford"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0058232.g006", "stats"=>{"downloads"=>8, "page_views"=>54, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Expression_levels_of_hp_Tau_and_PINCH_protein_in_frontal_cortex_brain_tissue_from_patients_/650529", "title"=>"Expression levels of hp-Tau and PINCH protein in frontal cortex brain tissue from patients.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-03-13 09:28:20"}
  • {"files"=>["https://ndownloader.figshare.com/files/985065"], "description"=>"<p>A) Representative Western blots of neurons uninfected (con), infected with shRNA against PINCH1 and 2 (shRNA P1/2) or non-target control shRNA with and without okadaic acid (OA) treatment. B) Quantification of protein expression levels of hp-Tau (AT8), and C) PINCH relative to loading control (GAPDH). No changes were detected in Hsp90, Hsp70 or CHIP. Results are from 4 separate experiments and are expressed as fold change over uninfected neurons (con). * p<0.005, **p<0.001 by one-way ANOVA with Tukey-Kramer post-hoc analyses.</p>", "links"=>[], "tags"=>["pinch", "hp-tau", "induction"], "article_id"=>650527, "categories"=>["Neuroscience", "Mental Health", "Infectious Diseases", "Molecular Biology", "Cell Biology"], "users"=>["Ahmet Yunus Ozdemir", "Inna Rom", "Jane Kovalevich", "William Yen", "Radhika Adiga", "Rajnish S. Dave", "Dianne Langford"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0058232.g005", "stats"=>{"downloads"=>1, "page_views"=>17, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Silencing_PINCH_during_hp_Tau_induction_results_in_less_hp_Tau_accumulation_/650527", "title"=>"Silencing PINCH during hp-Tau induction results in less hp-Tau accumulation.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-03-13 09:27:57"}

PMC Usage Stats | Further Information

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Relative Metric

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