Role of the microtubules in the electrical activity of the primary cilium of renal epithelial cells.

The primary cilium is a non-motile sensory organelle that transduces environmental cues into cellular responses. It comprises an axoneme, a core of nine doublet microtubules (MTs) coated by a specialized membrane populated by receptors, and a high density of ion channels. Dysfunctional primary cilia generate the pathogenesis of several diseases known as ciliopathies.

The bacterial tubulin homolog FtsZ generates electrical oscillations.

FtsZ, a major cytoskeletal protein in all bacteria and archaea, forms a ring that directs cytokinesis. Bacterial FtsZ is considered the ancestral homolog of the eukaryotic microtubule (MT)-forming tubulins, sharing GTPase activity and the ability to assemble into protofilaments, rings, and sheets, but not MTs. Previous studies from our laboratory demonstrated that structures of isolated brain MTs spontaneously generate electrical oscillations and bursts of electrical activity similar to action potentials.

The electrical properties of isolated microtubules.

This study examines the electrical properties of isolated brain microtubules (MTs), which are long hollow cylinders assembled from αβ-tubulin dimers that form cytoskeletal structures engaged in several functions. MTs are implicated in sensory functions in cilia and flagella and cellular activities that range from cell motility, vesicular traffic, and neuronal processes to cell division in the centrosomes and centrioles. We determined the electrical properties of the MTs with the loose patch clamp technique in either the presence or absence of the MT stabilizer Paclitaxel.

High calcium transport by Polycystin-2 (TRPP2) induces channel clustering and oscillatory currents.

The regulation by Ca of Ca-permeable ion channels represents an important mechanism in the control of cell function. Polycystin-2 (PC2, TRPP2), a member of the TRP channel family (Transient Potential Receptor), is a Ca permeable non-selective cation channel. Previous studies from our laboratory demonstrated that physiological concentrations of Ca do not regulate in vitro translated PC2 (PC2) channel activity.

Polycystin-2 (TRPP2) regulates primary cilium length in LLC-PK1 renal epithelial cells.

Polycystin-2 (PC2, TRPP2) is a Ca permeable nonselective cation channel whose dysfunction generates autosomal dominant polycystic kidney disease (ADPKD). PC2 is present in different cell locations, including the primary cilium of renal epithelial cells. However, little is known as to whether PC2 contributes to the primary cilium structure.

Brain Microtubule Electrical Oscillations-Empirical Mode Decomposition Analysis.

Microtubules (MTs) are essential cytoskeletal polymers of eukaryote cells implicated in various cell functions, including cell division, cargo transfer, and cell signaling. MTs also are highly charged polymers that generate electrical oscillations that may underlie their ability to act as nonlinear transmission lines. However, the oscillatory composition and time-frequency differences of the MT electrical oscillations have not been identified.

Electrical recordings from dendritic spines of adult mouse hippocampus and effect of the actin cytoskeleton.

Dendritic spines (DS) are tiny protrusions implicated in excitatory postsynaptic responses in the CNS. To achieve their function, DS concentrate a high density of ion channels and dynamic actin networks in a tiny specialized compartment. However, to date there is no direct information on DS ionic conductances.

Polycystin-2 (TRPP2): Ion channel properties and regulation.

Polycystin-2 (TRPP2, PKD2, PC2) is the product of the PKD2 gene, whose mutations cause Autosomal Dominant Polycystic Kidney Disease (ADPKD). PC2 belongs to the superfamily of TRP (Transient Receptor Potential) proteins that generally function as Ca-permeable nonselective cation channels implicated in Ca signaling. PC2 localizes to various cell domains with distinct functions that likely depend on interactions with specific channel partners.

Honeybee Brain Oscillations Are Generated by Microtubules. The Concept of a Brain Central Oscillator.

Microtubules (MTs) are important structures of the cytoskeleton in neurons. Mammalian brain MTs act as biomolecular transistors that generate highly synchronous electrical oscillations. However, their role in brain function is largely unknown.

Electrical behaviour and evolutionary computation in thin films of bovine brain microtubules.

We report on the electrical behaviour of thin films of bovine brain microtubules (MTs). For samples in both their dried and hydrated states, the measured currents reveal a power law dependence on the applied DC voltage. We attribute this to the injection of space-charge from the metallic electrode(s).

Actin filaments modulate electrical activity of brain microtubule protein two-dimensional sheets.

The cytoskeleton of eukaryotic cells contains networks of actin filaments and microtubules (MTs) that are jointly implicated in various cell functions, including cell division, morphogenesis, and migration. In neurons, this synergistic activity drives both the formation of axons during development and synaptic activity in mature neurons. Both actin filaments and MTs also are highly charged polyelectrolytes that generate and conduct electrical signals.

Two-Dimensional Brain Microtubule Structures Behave as Memristive Devices.

Microtubules (MTs) are cytoskeletal structures that play a central role in a variety of cell functions including cell division and cargo transfer. MTs are also nonlinear electrical transmission lines that produce and conduct electrical oscillations elicited by changes in either electric field and/or ionic gradients. The oscillatory behavior of MTs requires a voltage-sensitive gating mechanism to enable the electrodiffusional ionic movement through the MT wall.

Lipid bilayer-atomic force microscopy combined platform records simultaneous electrical and topological changes of the TRP channel polycystin-2 (TRPP2).

Ion channels are transmembrane proteins that mediate ion transport across biological membranes. Ion channel function is traditionally characterized by electrical parameters acquired with techniques such as patch-clamping and reconstitution in lipid bilayer membranes (BLM) that provide relevant information such as ionic conductance, selectivity, and gating properties. High resolution structural information of ion channels however, requires independent technologies, of which atomic force microscopy (AFM) is the only one that provides topological features of single functional channel proteins in their native environments.

Bundles of Brain Microtubules Generate Electrical Oscillations.

Microtubules (MTs) are long cylindrical structures of the cytoskeleton that control cell division, intracellular transport, and the shape of cells. MTs also form bundles, which are particularly prominent in neurons, where they help define axons and dendrites. MTs are bio-electrochemical transistors that form nonlinear electrical transmission lines.

External Ca regulates polycystin-2 (TRPP2) cation currents in LLC-PK1 renal epithelial cells.

Polycystin-2 (PC2, TRPP2) is a nonselective cation channel whose dysfunction is associated with the onset of autosomal dominant polycystic kidney disease (ADPKD). PC2 contributes to Ca transport and cell signaling in renal epithelia and other tissues. Little is known however, as to the external Ca regulation of PC2 channel function.

Electrical Oscillations in Two-Dimensional Microtubular Structures.

Microtubules (MTs) are unique components of the cytoskeleton formed by hollow cylindrical structures of αβ tubulin dimeric units. The structural wall of the MT is interspersed by nanopores formed by the lateral arrangement of its subunits. MTs are also highly charged polar polyelectrolytes, capable of amplifying electrical signals.

The cAMP Signaling Pathway and Direct Protein Kinase A Phosphorylation Regulate Polycystin-2 (TRPP2) Channel Function.

Polycystin-2 (PC2) is a TRP-type, Ca(2+)-permeable non-selective cation channel that plays an important role in Ca(2+) signaling in renal and non-renal cells. The effect(s) of the cAMP pathway and kinase mediated phosphorylation of PC2 seem to be relevant to PC2 trafficking and its interaction with polycystin-1. However, the role of PC2 phosphorylation in channel function is still poorly defined.

Polycystin-2 (TRPP2) Regulation by Ca(2+) Is Effected and Diversified by Actin-Binding Proteins.

Calcium regulation of Ca(2+)-permeable ion channels is an important mechanism in the control of cell function. Polycystin-2 (PC2, TRPP2), a member of the transient receptor potential superfamily, is a nonselective cation channel with Ca(2+) permeability. The molecular mechanisms associated with PC2 regulation by Ca(2+) remain ill-defined.

Calcium transport and local pool regulate polycystin-2 (TRPP2) function in human syncytiotrophoblast.

Polycystin-2 (PC2, TRPP2) is a Ca(2+)-permeable, nonselective cation channel implicated in Ca(2+) transport and epithelial cell signaling. Although PC2 may contribute to Ca(2+) transport in human term placenta, the regulatory mechanisms associated with Ca(2+) handling in this tissue are largely unknown. In this work we assessed the regulation by Ca(2+) of PC2 channel function from a preparation of apical membranes of human syncytiotrophoblast (PC2hst) reconstituted in a lipid bilayer system.

Structural interaction and functional regulation of polycystin-2 by filamin.

Filamins are important actin cross-linking proteins implicated in scaffolding, membrane stabilization and signal transduction, through interaction with ion channels, receptors and signaling proteins. Here we report the physical and functional interaction between filamins and polycystin-2, a TRP-type cation channel mutated in 10-15% patients with autosomal dominant polycystic kidney disease. Yeast two-hybrid and GST pull-down experiments demonstrated that the C-termini of filamin isoforms A, B and C directly bind to both the intracellular N- and C-termini of polycystin-2.

Effect of lithium on the electrical properties of polycystin-2 (TRPP2).

Polycystin-2 (PC2, TRPP2) is a TRP-type, non-selective cation channel whose dysfunction is implicated in changes in primary cilium structure and genesis of autosomal dominant polycystic kidney disease (ADPKD). Lithium (Li(+)) is a potent pharmaceutical agent whose effect on cell function is largely unknown. In this work, we explored the effect of Li(+) on PC2 channel function.

The multimeric structure of polycystin-2 (TRPP2): structural-functional correlates of homo- and hetero-multimers with TRPC1.

Polycystin-2 (PC2, TRPP2), the gene product of PKD2, whose mutations cause autosomal dominant polycystic kidney disease (ADPKD), belongs to the superfamily of TRP channels. PC2 is a non-selective cation channel, with multiple subconductance states. In this report, we explored structural and functional properties of PC2 and whether the conductance substates represent monomeric contributions to the channel complex.

Vasopressin receptor-mediated functional signaling pathway in primary cilia of renal epithelial cells.

The primary cilium of renal epithelial cells is a nonmotile sensory organelle, implicated in mechanosensory transduction signals. Recent studies from our laboratory indicate that renal epithelial primary cilia display abundant channel activity; however, the presence and functional role of specific membrane receptors in this organelle are heretofore unknown. Here, we determined a functional signaling pathway associated with the type 2 vasopressin receptor (V2R) in primary cilia of renal epithelial cells.