Primary Cilia and Calcium Signaling Interactions

Abstract

The calcium ion (Ca2+) is a diverse secondary messenger with a near-ubiquitous role in a vast array of cellular processes. Cilia are present on nearly every cell type in either a motile or non-motile form; motile cilia generate fluid flow needed for a variety of biological processes, such as left–right body patterning during development, while non-motile cilia serve as the signaling powerhouses of the cell, with vital singling receptors localized to their ciliary membranes. Much of the research currently available on Ca2+-dependent cellular actions and primary cilia are tissue-specific processes. However, basic stimuli-sensing pathways, such as mechanosensation, chemosensation, and electrical sensation (electrosensation), are complex processes entangled in many intersecting pathways; an overview of proposed functions involving cilia and Ca2+ interplay will be briefly summarized here. Next, we will focus on summarizing the evidence for their interactions in basic cellular activities, including the cell cycle, cell polarity and migration, neuronal pattering, glucose-mediated insulin secretion, biliary regulation, and bone formation. Literature investigating the role of cilia and Ca2+-dependent processes at a single-cellular level appears to be scarce, though overlapping signaling pathways imply that cilia and Ca2+ interact with each other on this level in widespread and varied ways on a perpetual basis. Vastly different cellular functions across many different cell types depend on context-specific Ca2+ and cilia interactions to trigger the correct physiological responses, and abnormalities in these interactions, whether at the tissue or the single-cell level, can result in diseases known as ciliopathies; due to their clinical relevance, pathological alterations of cilia function and Ca2+ signaling will also be briefly touched upon throughout this review.

Targeted Ablation of Primary Cilia in Differentiated Dopaminergic Neurons Reduces Striatal Dopamine and Responsiveness to Metabolic Stress

“…The primary cilium constitutes an electrophysiological micro-domain in neurons [ 20 , 60 , 61 ]. In highly vulnerable SN DA neurons, the PC might sense the metabolic state of the organism, e.g., by sensing extracellular glucose levels, as has been described for PC of pancreatic beta-cells [ 4 ], or by sensing intracellular calcium levels [ 62 ]. They might be important to adapt the ratio of dopamine-excited and dopamine-inhibited SN neurons to the current metabolic state.…”

IFT20 governs mesenchymal stem cell fate through positively regulating TGF-β-Smad2/3-Glut1 signaling mediated glucose metabolism

“…IFT proteins play critical roles in the bidirectional transport of molecules along cilia and are essential for cilia formation and function [ [30] , [31] , [32] ]. Disruption of primary cilia and ciliary protein results in abnormal skeletal development and remodeling [ 9 , 30 , 31 ].…”

Pharmacological intervention of the FGF-PTH axis as a potential therapeutic for craniofacial ciliopathies

“…Calcium signaling plays a pivotal role during bone development, and depleted calcium uptake is the main cause of conditions such as osteoporosis and rickets (Monsen, 1989). There is no consensus as to if the primary cilium plays a major role in calcium signaling (Delaine-Smith et al, 2014;Delling et al, 2013;Delling et al, 2016;Hoey et al, 2012;Lee et al, 2015;Malone et al, 2007;Saternos et al, 2020), yet our results support a systemic role for cilia in the differentiation of osteoblasts (Bonatto Paese et al, 2021). It is possible that the role of cilia in calcium uptake may vary between tissues (e.g., node vs. osteoblast), temporally during development, or between chemosensory and mechanosensory cilia.…”