title: Activation of the cAMP Pathway Induces RACK1-Dependent Binding of β-Actin to BDNF Promoter.
abstract: RACK1 is a scaffolding protein that contributes to the specificity and propagation of several signaling cascades including the cAMP pathway. As such, RACK1 participates in numerous cellular functions ranging from cell migration and morphology to gene transcription. To obtain further insights on the mechanisms whereby RACK1 regulates cAMP-dependent processes, we set out to identify new binding partners of RACK1 during activation of the cAMP signaling using a proteomics strategy. We identified β-actin as a direct RACK1 binding partner and found that the association between β-actin and RACK1 is increased in response to the activation of the cAMP pathway. Furthermore, we show that cAMP-dependent increase in BDNF expression requires filamentous actin. We further report that β-actin associates with the BDNF promoter IV upon the activation of the cAMP pathway and present data to suggest that the association of β-actin with BDNF promoter IV is RACK1-dependent. Taken together, our data suggest that β-actin is a new RACK1 binding partner and that the RACK1 and β-actin association participate in the cAMP-dependent regulation of BDNF transcription.
authors: Department of Neurology, University of California, San Francisco, California, United States of America.
authors: Jeremie
authors: J
authors: Neasta
authors: Department of Neurology, University of California, San Francisco, California, United States of America.
authors: Anna
authors: A
authors: Fiorenza
authors: Department of Neurology, University of California, San Francisco, California, United States of America.
authors: Dao-Yao
authors: DY
authors: He
authors: Department of Neurology, University of California, San Francisco, California, United States of America.
authors: Khanhky
authors: K
authors: Phamluong
authors: Graduate Entry Medical School, Health Research Institute and Materials and Surface Science Institute, University of Limerick, Limerick, Ireland.
authors: Patrick A
authors: PA
authors: Kiely
authors: Department of Neurology, University of California, San Francisco, California, United States of America.
authors: Dorit
authors: D
authors: Ron
mesh_terms: D008841:Actin Cytoskeleton / Q000378:metabolism; D000199:Actins / Q000378:metabolism*; D019208:Brain-Derived Neurotrophic Factor / Q000235:genetics*; D045744:Cell Line, Tumor; D002467:Cell Nucleus / Q000378:metabolism; D000242:Cyclic AMP / Q000378:metabolism*; D019204:GTP-Binding Proteins / Q000378:metabolism*; D006801:Humans; D009363:Neoplasm Proteins / Q000378:metabolism*; D011401:Promoter Regions, Genetic / Q000235:genetics*; D011485:Protein Binding; D021381:Protein Transport; D000075370:Receptors for Activated C Kinase; D011956:Receptors, Cell Surface / Q000378:metabolism*; D015398:Signal Transduction; D014158:Transcription, Genetic
chemical_list: D000199:Actins; D019208:Brain-Derived Neurotrophic Factor; D009363:Neoplasm Proteins; C419368:RACK1 protein, human; D000075370:Receptors for Activated C Kinase; D011956:Receptors, Cell Surface; D000242:Cyclic AMP; D019204:GTP-Binding Proteins