" The primary cilium is a non-motile sensory organelle that acts as a transducer of environmental cues into cellular responses. It comprises an axoneme, which is a core of microtubules (MTs), coated by a specialized membrane populated by receptors and a high density of ion channels. Dysfunctional primary cilia generate several diseases known as ciliopathies. However, the nature of ciliary signaling remains largely unknown. Herein, we determined by the patch-clamp technique, the electrical activity of cytoplasmic and axonemal MTs from LLC-PK1 renal epithelial cells. We observed electrical oscillations with fundamental frequencies at ~39 Hz and ~93 Hz in sheets of cytoplasmic MTs. We also studied isolated and in situ intact and Triton X-permeabilized primary cilia, observing electrical oscillations with peak frequencies at either 29-49 (non-permeabilized) or ~40-49 Hz (permeabilized) and ~93 Hz (both). The axonemal electrical oscillations changed with maneuvers that modify ciliary length, including addition of external Ca2+ and Li+. We also applied Continuous Wavelet Transform (CWT) and cross-correlation analyses in the Time-Frequency domain to assess the coherence between cytoplasmic and axonemal MT electrical oscillations. The evidence indicates that the primary cilium is an electrical antenna that produces MT-based electrical oscillations regulated by ciliary channels and receptors." {Credits 1} " The primary cilium is a sensory organelle that protrudes from the center of most eukaryotic cells, particularly renal epithelial cells [1]. Mobile cilia, also known as flagella, distinguish from primary cilia because of their ciliary microtubules (MTs) pattern. Mobile cilia and flagella are found in lower eukaryotes and specialized cell types such as sperm. The axoneme of mobile cilia is constituted by nine doublets of peripheral MTs surrounding two individual central MTs (9 + 2) [1]. Primary cilia have a 9 + 0 pattern. Changes in shape and the loss of motility facilitated diversification of ciliary function into sensory properties. Primary cilia such as those found in the brain or olfactory epithelium are typically rod or whip-shaped. Other specialized cilia, such as those found in vertebrate rods and cone photoreceptors, have elaborate distal ciliary segments. The functional plasticity of primary cilia as sensory organelles has developed in both metazoans and vertebrates to include the transduction of many environmental signals. With few exceptions, such as lymphocytes and intercalar cells of the distal nephron, all cells express one or more primary cilia at some point in their cell cycle." {Credits 1} " Previous studies from our laboratory showed that different mammalian brain MT structures including 2D-sheets and bundles generate strong electrical oscillations [22, 23] that resemble those observed in isolated MTs [24]." {Credits 1} " Our findings indicate that the axoneme generates endogenous electrical oscillations different from those elicited by the cytoplasmic MTs, indicating that the primary cilium arranges its axonemal MTs to produce a frame of electrical oscillators that behave as an electrical antenna." {Credits 1} " Our present findings incorporate the first cytoskeletal structure to contribute to the electrical activity of the organelle (Fig. 9), and demonstrate that the ciliary axoneme behaves as an active antenna capable of oscillatory amplification and frequency modulation, shifting the frequency peaks to provide the basis for a novel electrical intracellular signaling mechanism that targets the cellular compartment. The process is consistent with the coherent synchronization of oscillators and random antennas [69, 70, 71]." {Credits 1} {Credits 1} 🎪 Horacio F Cantiello, Noelia Scarinci, Brenda C Gutierrez et al. The Primary Cilium is a Microtubule-Driven Electrical Antenna. The Case of Renal Epithelial Cells, 23 February 2022, PREPRINT (Version 1) available at Research Square [https://doi.org/10.21203/rs.3.rs-1346209/v1]. © 2022 The Author(s). This is an open access article distributed under the terms of the Creative Commons Attribution License 4.0. |
Last modified on 11-Nov-24 |