Activation of the cAMP Pathway Induces RACK1-Dependent Binding of beta-Actin to BDNF Promoter

作者：Neasta Jeremie; Fiorenza Anna; He Dao Yao; Phamluong Khanhky; Kiely Patrick A; Ron Dorit^*

来源：PLos One, 2016, 11(8): e0160948.

DOI：10.1371/journal.pone.0160948

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 beta-actin as a direct RACK1 binding partner and found that the association between beta-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 beta-actin associates with the BDNF promoter IV upon the activation of the cAMP pathway and present data to suggest that the association of beta-actin with BDNF promoter IV is RACK1-dependent. Taken together, our data suggest that beta-actin is a new RACK1 binding partner and that the RACK1 and beta-actin association participate in the cAMP-dependent regulation of BDNF transcription.

• 出版日期2016-8-9