Acidosis-induced V-ATPase trafficking in salivary ducts is initiated by cAMP/PKA/CREB pathway via regulation of Rab11b expression

The International Journal of Biochemistry & Cell Biology
Oliver OehlkeEleni Roussa

Abstract

Changes in systemic acid-base homeostasis cause a series of organ-specific cellular responses, among them changes of acid-base transporter activities, and recruitment or retrieval of these transporters from intracellular pools to the plasma membrane and vice versa. The purpose of this study was to investigate the impact of protein phosphorylation in the acidosis-induced translocation of vacuolar-type H(+)-ATPase (V-ATPase) in salivary ducts and to identify molecular targets. Therefore, the human submandibular gland cell line HSG was exposed to acidosis and V-ATPase trafficking was investigated in the presence or absence of inhibitors and activators of sAC/PKA and Src/ERK signaling pathways. Putative target genes have been identified by RT-PCR and immunoblotting, and validated by loss-of-function experiments. Acidosis caused activation of cAMP/PKA and Src signaling and inhibition of either pathway significantly impaired acidosis-induced V-ATPase redistribution and incorporation into the plasma membrane. Activation of ERK1/2 was Src-independent, whereas activation of PKA caused phosphorylation of cAMP response element-binding (CREB) and activation to regulate Rab11b transcription. Loss-of-function of CREB down-regulated Rab11b tr...Continue Reading

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Citations

Jun 28, 2014·Biochimica Et Biophysica Acta·Martin Tresguerres
Feb 25, 2014·Communicative & Integrative Biology·Flaviano Giorgini, Joern R Steinert
Nov 17, 2017·Molecular Membrane Biology·Bor Luen Tang
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Oct 14, 2021·Cancer Cell International·Tianyu ZhengBin Liu

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