APP deficiency selectively reduces Nav1.6-mediated Na<sup>+</sup> currents in cerebellar PCs.
<p><b>(A)</b> Representative traces for whole-cell recording of transient Na<sup>+</sup> currents (<i>I</i><sub>Na</sub>) in PCs of <i>App</i><sup>+/+</sup> or <i>App</i><sup>−/−</sup> mice. <b&g...
Wedi'i Gadw mewn:
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2025
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Ychwanegu Tag
Dim Tagiau, Byddwch y cyntaf i dagio'r cofnod hwn!
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| _version_ | 1849927642295304192 |
|---|---|
| author | Miao-Jin Ji (22676552) |
| author2 | Tong-Xuan Wu (22676555) Chenhao Tian (10801643) Xiang Cao (298023) Ruyuan Wei (22676558) Yin-Yin Yang (301866) Xinran Meng (11537536) Huanyao Tang (22676561) Tiantao Cui (22676564) Jiao Yang (623531) Xin Tang (134573) Chao Liu (43092) |
| author2_role | author author author author author author author author author author author |
| author_facet | Miao-Jin Ji (22676552) Tong-Xuan Wu (22676555) Chenhao Tian (10801643) Xiang Cao (298023) Ruyuan Wei (22676558) Yin-Yin Yang (301866) Xinran Meng (11537536) Huanyao Tang (22676561) Tiantao Cui (22676564) Jiao Yang (623531) Xin Tang (134573) Chao Liu (43092) |
| author_role | author |
| dc.creator.none.fl_str_mv | Miao-Jin Ji (22676552) Tong-Xuan Wu (22676555) Chenhao Tian (10801643) Xiang Cao (298023) Ruyuan Wei (22676558) Yin-Yin Yang (301866) Xinran Meng (11537536) Huanyao Tang (22676561) Tiantao Cui (22676564) Jiao Yang (623531) Xin Tang (134573) Chao Liu (43092) |
| dc.date.none.fl_str_mv | 2025-11-24T18:30:33Z |
| dc.identifier.none.fl_str_mv | 10.1371/journal.pbio.3003513.g004 |
| dc.relation.none.fl_str_mv | https://figshare.com/articles/figure/APP_deficiency_selectively_reduces_Nav1_6-mediated_Na_sup_sup_currents_in_cerebellar_PCs_/30697280 |
| dc.rights.none.fl_str_mv | CC BY 4.0 info:eu-repo/semantics/openAccess |
| dc.subject.none.fl_str_mv | Biochemistry Cell Biology Molecular Biology Neuroscience Physiology Developmental Biology Infectious Diseases mediated sodium currents deep cerebellar nucleus aberrant firing patterns specific app reconstitution cerebellar motor control app deficiency leads electrophysiological analysis revealed 6 channel activity motor performance motor function motor deficits app selectively purkinje cells marked reduction impaired locomotion findings reveal exogenous expression essential role dcn ). conditional knockdown behavioral deficits |
| dc.title.none.fl_str_mv | APP deficiency selectively reduces Nav1.6-mediated Na<sup>+</sup> currents in cerebellar PCs. |
| dc.type.none.fl_str_mv | Image Figure info:eu-repo/semantics/publishedVersion image |
| description | <p><b>(A)</b> Representative traces for whole-cell recording of transient Na<sup>+</sup> currents (<i>I</i><sub>Na</sub>) in PCs of <i>App</i><sup>+/+</sup> or <i>App</i><sup>−/−</sup> mice. <b>(B)</b> Whole cell <i>I</i>–<i>V</i> curve, peak currents, and activation curves of transient I<sub>Na</sub> as shown in (A). <i>App</i><sup>+/+</sup>, <i>n</i> = 8; <i>App</i><sup>−/−</sup>, <i>n</i> = 14 cells. <b>(C, D)</b> Representative traces and statistical bar-charts showing amplitude of transient <i>I</i><sub>Na</sub> (<i>I</i><sub>NaT</sub>) before or during bath application of (C) Nav1.6-specific blocker 4,9-anhydrotetrodotoxin (4,9-ahTTX, 200 nM) or (D) Nav1.1-specific inhibitor ICA-121431 (ICA, 350 nM). <i>N</i> = 6 cells for each group. The <i>I</i><sub>Na1.6</sub> or <i>I</i><sub>Na1.1</sub> were determined by subtracting the sodium currents recorded during bath application of specific blockers/inhibitors from that before drug application. <b>(E)</b> Representative persistent Na<sup>+</sup> currents recorded in PCs. The right panels show statistics of the peak persistent currents and voltage potentials eliciting peak persistent Na<sup>+</sup> currents. <i>App</i><sup>+/+</sup>, <i>n</i> = 6; <i>App</i><sup>−/−</sup>, <i>n</i> = 12 cells. <b>(F)</b> Representative traces (the left panel) and statistics for whole-cell recording of resurgent <i>I</i><sub>Na</sub> in PCs. The middle panel: Whole cell <i>I</i>–<i>V</i> curve of resurgent <i>I</i><sub>Na</sub>; the right panel: peak resurgent currents. <i>App</i><sup>+/+</sup>, <i>n</i> = 9; <i>App</i><sup>−/−</sup>, <i>n</i> = 11 cells. Student <i>t</i> test; * <i>P</i> < 0.05; ** <i>P</i> < 0.01; ns, nonsignificant. Scale bars are indicated in the images. <b>(G)</b> APP co-immunoprecipitated with Nav1.6 but not Nav1.1. HEK293 cells co-expressing Flag-tagged APP and either Nav1.6 or Nav1.1-EGFP were lysed and immunoprecipitated (IP) with anti-Flag affinity beads (Smart-Lifesciences, #SA042001). Immunoblots (IB) were probed for: Nav1.6 (Alomone Labs #ASC-009), EGFP (Roche Applied Science, #11814460001) or Flag (AlpVHHs, #016-303-005). <b>(H)</b> Nav1.6 interacts with full-length APP (holo-APP), but not soluble APPα (sAPPα) and APP intracellular domain (AICD). HEK293 cells co-expressing Nav1.6 and Flag-tagged holo-APP, sAPPα, or AICD were lysed and IPed with anti-Flag affinity beads. IB were probed for Nav1.6 or Flag. Mock transfected controls are shown in the first lane. Input controls (7.5% lysate) shown below/beside corresponding lanes. Data representative of 3 biological replicates. The data underlying this Figure can be found in <a href="http://www.plosbiology.org/article/info:doi/10.1371/journal.pbio.3003513#pbio.3003513.s011" target="_blank">S1 Data</a>.</p> |
| eu_rights_str_mv | openAccess |
| id | Manara_8257f580b2e0b11d9e191c122ff15c32 |
| identifier_str_mv | 10.1371/journal.pbio.3003513.g004 |
| network_acronym_str | Manara |
| network_name_str | ManaraRepo |
| oai_identifier_str | oai:figshare.com:article/30697280 |
| publishDate | 2025 |
| repository.mail.fl_str_mv | |
| repository.name.fl_str_mv | |
| repository_id_str | |
| rights_invalid_str_mv | CC BY 4.0 |
| spelling | APP deficiency selectively reduces Nav1.6-mediated Na<sup>+</sup> currents in cerebellar PCs.Miao-Jin Ji (22676552)Tong-Xuan Wu (22676555)Chenhao Tian (10801643)Xiang Cao (298023)Ruyuan Wei (22676558)Yin-Yin Yang (301866)Xinran Meng (11537536)Huanyao Tang (22676561)Tiantao Cui (22676564)Jiao Yang (623531)Xin Tang (134573)Chao Liu (43092)BiochemistryCell BiologyMolecular BiologyNeurosciencePhysiologyDevelopmental BiologyInfectious Diseasesmediated sodium currentsdeep cerebellar nucleusaberrant firing patternsspecific app reconstitutioncerebellar motor controlapp deficiency leadselectrophysiological analysis revealed6 channel activitymotor performancemotor functionmotor deficitsapp selectivelypurkinje cellsmarked reductionimpaired locomotionfindings revealexogenous expressionessential roledcn ).conditional knockdownbehavioral deficits<p><b>(A)</b> Representative traces for whole-cell recording of transient Na<sup>+</sup> currents (<i>I</i><sub>Na</sub>) in PCs of <i>App</i><sup>+/+</sup> or <i>App</i><sup>−/−</sup> mice. <b>(B)</b> Whole cell <i>I</i>–<i>V</i> curve, peak currents, and activation curves of transient I<sub>Na</sub> as shown in (A). <i>App</i><sup>+/+</sup>, <i>n</i> = 8; <i>App</i><sup>−/−</sup>, <i>n</i> = 14 cells. <b>(C, D)</b> Representative traces and statistical bar-charts showing amplitude of transient <i>I</i><sub>Na</sub> (<i>I</i><sub>NaT</sub>) before or during bath application of (C) Nav1.6-specific blocker 4,9-anhydrotetrodotoxin (4,9-ahTTX, 200 nM) or (D) Nav1.1-specific inhibitor ICA-121431 (ICA, 350 nM). <i>N</i> = 6 cells for each group. The <i>I</i><sub>Na1.6</sub> or <i>I</i><sub>Na1.1</sub> were determined by subtracting the sodium currents recorded during bath application of specific blockers/inhibitors from that before drug application. <b>(E)</b> Representative persistent Na<sup>+</sup> currents recorded in PCs. The right panels show statistics of the peak persistent currents and voltage potentials eliciting peak persistent Na<sup>+</sup> currents. <i>App</i><sup>+/+</sup>, <i>n</i> = 6; <i>App</i><sup>−/−</sup>, <i>n</i> = 12 cells. <b>(F)</b> Representative traces (the left panel) and statistics for whole-cell recording of resurgent <i>I</i><sub>Na</sub> in PCs. The middle panel: Whole cell <i>I</i>–<i>V</i> curve of resurgent <i>I</i><sub>Na</sub>; the right panel: peak resurgent currents. <i>App</i><sup>+/+</sup>, <i>n</i> = 9; <i>App</i><sup>−/−</sup>, <i>n</i> = 11 cells. Student <i>t</i> test; * <i>P</i> < 0.05; ** <i>P</i> < 0.01; ns, nonsignificant. Scale bars are indicated in the images. <b>(G)</b> APP co-immunoprecipitated with Nav1.6 but not Nav1.1. HEK293 cells co-expressing Flag-tagged APP and either Nav1.6 or Nav1.1-EGFP were lysed and immunoprecipitated (IP) with anti-Flag affinity beads (Smart-Lifesciences, #SA042001). Immunoblots (IB) were probed for: Nav1.6 (Alomone Labs #ASC-009), EGFP (Roche Applied Science, #11814460001) or Flag (AlpVHHs, #016-303-005). <b>(H)</b> Nav1.6 interacts with full-length APP (holo-APP), but not soluble APPα (sAPPα) and APP intracellular domain (AICD). HEK293 cells co-expressing Nav1.6 and Flag-tagged holo-APP, sAPPα, or AICD were lysed and IPed with anti-Flag affinity beads. IB were probed for Nav1.6 or Flag. Mock transfected controls are shown in the first lane. Input controls (7.5% lysate) shown below/beside corresponding lanes. Data representative of 3 biological replicates. The data underlying this Figure can be found in <a href="http://www.plosbiology.org/article/info:doi/10.1371/journal.pbio.3003513#pbio.3003513.s011" target="_blank">S1 Data</a>.</p>2025-11-24T18:30:33ZImageFigureinfo:eu-repo/semantics/publishedVersionimage10.1371/journal.pbio.3003513.g004https://figshare.com/articles/figure/APP_deficiency_selectively_reduces_Nav1_6-mediated_Na_sup_sup_currents_in_cerebellar_PCs_/30697280CC BY 4.0info:eu-repo/semantics/openAccessoai:figshare.com:article/306972802025-11-24T18:30:33Z |
| spellingShingle | APP deficiency selectively reduces Nav1.6-mediated Na<sup>+</sup> currents in cerebellar PCs. Miao-Jin Ji (22676552) Biochemistry Cell Biology Molecular Biology Neuroscience Physiology Developmental Biology Infectious Diseases mediated sodium currents deep cerebellar nucleus aberrant firing patterns specific app reconstitution cerebellar motor control app deficiency leads electrophysiological analysis revealed 6 channel activity motor performance motor function motor deficits app selectively purkinje cells marked reduction impaired locomotion findings reveal exogenous expression essential role dcn ). conditional knockdown behavioral deficits |
| status_str | publishedVersion |
| title | APP deficiency selectively reduces Nav1.6-mediated Na<sup>+</sup> currents in cerebellar PCs. |
| title_full | APP deficiency selectively reduces Nav1.6-mediated Na<sup>+</sup> currents in cerebellar PCs. |
| title_fullStr | APP deficiency selectively reduces Nav1.6-mediated Na<sup>+</sup> currents in cerebellar PCs. |
| title_full_unstemmed | APP deficiency selectively reduces Nav1.6-mediated Na<sup>+</sup> currents in cerebellar PCs. |
| title_short | APP deficiency selectively reduces Nav1.6-mediated Na<sup>+</sup> currents in cerebellar PCs. |
| title_sort | APP deficiency selectively reduces Nav1.6-mediated Na<sup>+</sup> currents in cerebellar PCs. |
| topic | Biochemistry Cell Biology Molecular Biology Neuroscience Physiology Developmental Biology Infectious Diseases mediated sodium currents deep cerebellar nucleus aberrant firing patterns specific app reconstitution cerebellar motor control app deficiency leads electrophysiological analysis revealed 6 channel activity motor performance motor function motor deficits app selectively purkinje cells marked reduction impaired locomotion findings reveal exogenous expression essential role dcn ). conditional knockdown behavioral deficits |