Cilia are minuscule hair-like projections rising out of most cells in the body. Among these cellular protrusions known as cilia, some can generate movement, rotate or flick while the primary cilia sway helplessly to the flow of the external milieu surrounding the cells. They are simplistic in a physical sense, especially when you consider the primary cilia. The primary cilia bend to the flow of the blood in the vessels. If the flow increases, so does the bending of the cilia. From this perspective, the cilia are poised to be a perfect biosensor for mechanical cues such as blood flow but also potentially for the chemical environment. The ciliary membrane is enriched with various receptors, ion channels while the interior is a highly regulated machinery that makes the cilia an important signaling nexus of the cell. Studies have attributed the cilia to be a pathway to activate intracellular signaling cascades that regulate cellular processes including ion transport, gene expression, cell proliferation, and/or cell death. So great is the impact of the cilia that more than a dozen disorders arising from ciliary dysfunction or absence are collectively called ciliopathies.

Fig. 1. The role of primary cilia in pH Sensing.
Changes in the vascular endothelia when pH decreases. Acidosis causes activation of MAP kinases and the cells counter the pH decrease with potassium dependent mechanisms. The drop in pH also increases ciliary length which could either be a marker for cell stress or a functionally significant modification to the cilia.

Numerous studies have looked into the role of primary cilia as a flow sensor but one very possible and critical role could be in sensing blood pH. Similar to a probe, the cilia extend into the blood vessel and could detect the pH levels and regulate the acid response in cells. The typical blood pH level is maintained between 7.35 and 7.45 by the renal and respiratory systems along with buffering mediators in the blood. Lowering of blood pH less than 7.35 or acidosis causes several symptoms such as exhaustion, and arrhythmia depending on the type of acidosis while dramatic changes in pH will induce cytotoxicity and neuronal cell death. This study would nonetheless add to the growing knowledge trying to define the role of primary cilia in vascular diseases. Using endothelial cells which are the inner lining of blood vessels and a pH-sensitive 2′,7′-biscarboxyethy1-5,6-carboxyfluorescein acetoxy-methylester (BCECF) fluorescent indicator, acidic conditions were created to detect responses of the cell. As a comparison, genetically modified cells without cilia were tested as well. Although the absence of cilia did not affect the overall response of the cell to the pH change, the cilia less cell was slower to activate ERK1/2 and p38-mediated signaling pathways. These endothelial cells respond to pH changes with a predominantly potassium dependent recovery mechanism, regardless of ciliary presence or absence (Fig. 1).

Although the primary cilia did not turn out to be critical sensors of pH in the blood, the acidic environment did cause a change to the length of primary cilia. Lengthening of the cilia makes the cilia more sensitive to fluid flow. This response could be due to the acidic pH mediated activation of ERK1/2 and p38-mediated signaling pathways. It has also been speculated that cilia length could represent the cell responding to injury or environmental insults such as acidosis. These observations would require further research to establish any functional consequence of the acid-mediated ciliary length increase.

Rinzhin T Sherpa, Kimberly F Atkinson, Surya M Nauli
Department of Biomedical & Pharmaceutical Sciences, Chapman University, Irvine, CA 92618, USA
Department of Medicine, Division of Nephrology, University of California Irvine, Irvine, CA 92697, USA
Department of Pharmacology, University of Nevada, Reno, NV 89557, USA

Publication

The Role of the Primary Cilium in Sensing Extracellular pH
Kimberly F Atkinson, Rinzhin T Sherpa, Surya M Nauli
Cells. 2019 Jul 11

Read offline:     

Related Articles:

	Ti3C2-MXene based fluorescent biosensor for rapid… Over the last decade, zero-dimensional (0D) and two-dimensional (2D) nanomaterials such as nanostructured metals, and graphene derivatives delivered an extraordinary impact as fluorescence quenchers or energy acceptors in developing fluorescent…
	Murburn concept explains why oxygen is acutely… Murburn concept (from “mured burning”, signifying a restricted uncontrolled oxidative process) provides a tangible rationale why oxygen is so quintessential for immediate maintenance of life-order. It postulates that oxygen-centered diffusible…
	The complex regulation and functional significance… Across animals, variation in body size is often influenced by environmental conditions and is considered to have adaptive value. In bees, in which many species show various degrees of sociality,…
	Ultra-wideband absorption based on… Due to high carrier mobility, the graphene has attracted enormous interests in developing high-speed photodetectors. In this study, for practical high-performance photodetectors, we focus on the remarkable enlargement of absorption…
	The SETOC: Visualizing carcinogenesis through a… The Systemic-Evolutionary Theory of the Origin of Cancer (SETOC) is a recently proposed theory based on two fundamental principles: (i) Margulian evolution as a process of cooperation and endosymbiosis and…
	Your pharmacist will see you now! Public perception of pharmacists might be limited to dispensing medications. However, pharmacists are trained to deliver patient care to help patients improve their health-related outcomes and achieve their goals. Recognizing…