دورية أكاديمية
AKAP79/150 recruits the transcription factor NFAT to regulate signaling to the nucleus by neuronal L-type Ca 2+ channels.
| العنوان: | AKAP79/150 recruits the transcription factor NFAT to regulate signaling to the nucleus by neuronal L-type Ca 2+ channels. |
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| المؤلفون: | Murphy JG; Eunice Kennedy Shriver Institute for Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892.; Department of Pharmacology, University of Colorado School of Medicine, Aurora, CO 80045., Crosby KC; Department of Pharmacology, University of Colorado School of Medicine, Aurora, CO 80045., Dittmer PJ; Department of Pharmacology, University of Colorado School of Medicine, Aurora, CO 80045., Sather WA; Department of Pharmacology, University of Colorado School of Medicine, Aurora, CO 80045., Dell'Acqua ML; Department of Pharmacology, University of Colorado School of Medicine, Aurora, CO 80045. |
| المصدر: | Molecular biology of the cell [Mol Biol Cell] 2019 Jul 01; Vol. 30 (14), pp. 1743-1756. Date of Electronic Publication: 2019 May 15. |
| نوع المنشور: | Journal Article; Research Support, N.I.H., Extramural |
| اللغة: | English |
| بيانات الدورية: | Publisher: American Society for Cell Biology Country of Publication: United States NLM ID: 9201390 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1939-4586 (Electronic) Linking ISSN: 10591524 NLM ISO Abbreviation: Mol Biol Cell Subsets: MEDLINE |
| أسماء مطبوعة: | Original Publication: Bethesda, MD : American Society for Cell Biology, c1992- |
| مواضيع طبية MeSH: | Signal Transduction*, A Kinase Anchor Proteins/*metabolism , Calcium Channels, L-Type/*metabolism , Cell Nucleus/*metabolism , NFATC Transcription Factors/*metabolism , Neurons/*metabolism, A Kinase Anchor Proteins/chemistry ; Amino Acid Motifs ; Animals ; Calcineurin/metabolism ; Calcium Signaling ; Cell Line ; Cells, Cultured ; Cyclic AMP-Dependent Protein Kinases/metabolism ; Dendritic Spines/metabolism ; Hippocampus/cytology ; Models, Biological ; Protein Binding ; Protein Transport ; Rats, Sprague-Dawley ; Transcription, Genetic |
| مستخلص: | In neurons, regulation of activity-dependent transcription by the nuclear factor of activated T-cells (NFAT) depends upon Ca 2+ influx through voltage-gated L-type calcium channels (LTCC) and NFAT translocation to the nucleus following its dephosphorylation by the Ca 2+ -dependent phosphatase calcineurin (CaN). CaN is recruited to the channel by A-kinase anchoring protein (AKAP) 79/150, which binds to the LTCC C-terminus via a modified leucine-zipper (LZ) interaction. Here we sought to gain new insights into how LTCCs and signaling to NFAT are regulated by this LZ interaction. RNA interference-mediated knockdown of endogenous AKAP150 and replacement with human AKAP79 lacking its C-terminal LZ domain resulted in loss of depolarization-stimulated NFAT signaling in rat hippocampal neurons. However, the LZ mutation had little impact on the AKAP-LTCC interaction or LTCC function, as measured by Förster resonance energy transfer, Ca 2+ imaging, and electrophysiological recordings. AKAP79 and NFAT coimmunoprecipitated when coexpressed in heterologous cells, and the LZ mutation disrupted this association. Critically, measurements of NFAT mobility in neurons employing fluorescence recovery after photobleaching and fluorescence correlation spectroscopy provided further evidence for an AKAP79 LZ interaction with NFAT. These findings suggest that the AKAP79/150 LZ motif functions to recruit NFAT to the LTCC signaling complex to promote its activation by AKAP-anchored calcineurin. |
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| معلومات مُعتمدة: | P30 NS048154 United States NS NINDS NIH HHS; R01 MH102338 United States MH NIMH NIH HHS; UL1 TR001082 United States TR NCATS NIH HHS |
| المشرفين على المادة: | 0 (A Kinase Anchor Proteins) 0 (AKAP5 protein, human) 0 (Calcium Channels, L-Type) 0 (NFATC Transcription Factors) EC 2.7.11.11 (Cyclic AMP-Dependent Protein Kinases) EC 3.1.3.16 (Calcineurin) |
| تواريخ الأحداث: | Date Created: 20190516 Date Completed: 20200108 Latest Revision: 20200309 |
| رمز التحديث: | 20231215 |
| مُعرف محوري في PubMed: | PMC6727748 |
| DOI: | 10.1091/mbc.E19-01-0060 |
| PMID: | 31091162 |
| قاعدة البيانات: | MEDLINE |
| تدمد: | 1939-4586 |
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| DOI: | 10.1091/mbc.E19-01-0060 |