The Role of the Primary Cilium in Sensing Extracellular pH

Authors

Kimberly F. Atkinson, Chapman University
Rinzhin T. Sherpa, Chapman University
Surya M. Nauli, Chapman UniversityFollow

Document Type

Article

Publication Date

7-11-2019

Abstract

Biosensors on the membrane of the vascular endothelium are responsible for sensing mechanical and chemical signals in the blood. Transduction of these stimuli into intracellular signaling cascades regulate cellularprocesses including ion transport, gene expression, cellproliferation, and/or cell death. The primary cilium is a well-known biosensor of shear stress but its role in sensing extracellular pH change has never been examined. As a cellular extension into the immediate microenvironment, the ciliumcould be a prospective sensor for changes in pHand regulator of acid response in cells. We aim to test our hypothesis that the primary cilium plays the role of an acid sensor in cells using vascular endothelial and embryonic fibroblast cells as in vitro models. We measure changes in cellular pH using pH-sensitive 2',7'-biscarboxyethy1-5,6-carboxyfluorescein acetoxy-methylester (BCECF) fluorescence and mitogen-activated protein kinase (MAPK) activity to quantify responses to both extracellular pH (pH_o) and intracellular pH (pH_i) changes. Our studies show that changes in pH_o affect pH_i in both wild-type and cilia-less Tg737 cells and that the kinetics of the pH_i response are similar in both cells. Acidic pH_o or pH_i was observed to change the length of primary cilia in wild-type cells while the cilia in Tg737 remained absent. Vascular endothelial cells respond to acidic pH through activation of ERK1/2 and p38-mediated signaling pathways. The cilia-less Tg737 cells exhibit delayed responsiveness to pHo dependent and independent pH_i acidification as depicted in the phosphorylation profile of ERK1/2 and p38. Otherwise, intracellular pH homeostatic response to acidic pH_o is similar between wild-type and Tg737 cells, indicating that the primary cilia may not be the sole sensor for physiological pH changes. These endothelial cells respond to pH changes with a predominantly K+-dependent pH_i recovery mechanism, regardless of ciliary presence or absence.

Comments

This article was originally published in Cells, volume 8, in 2019. DOI: 10.3390/cells8070704

Recommended Citation

Atkinson KF, Sherpa RT, Nauli SM. The role of the primary cilium in sensing extracellular pH. Cells. 2019;8:704. doi:10.3390/cells8070704

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This work is licensed under a Creative Commons Attribution 4.0 License.