Mechanisms regulating cilia growth and cilia function in endothelial cells

Abdul-Majeed, Shakila; Moloney, Bryan C.; Nauli, Surya M.

doi:10.1007/s00018-011-0744-0

Cited by 75 publications

(79 citation statements)

References 31 publications

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“…Cyclic AMP signaling has been reported to positively regulate cilia length in several cell types including OSNs [13, 30, 31]. We therefore asked whether odor-induced cAMP signaling is required for establishing the cilia pattern.…”

Section: Resultsmentioning

confidence: 99%

An Olfactory Cilia Pattern in the Mammalian Nose Ensures High Sensitivity to Odors

et al. 2015

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Summary In many sensory organs, specialized receptors are strategically arranged to enhance detection sensitivity and acuity. It is unclear whether the olfactory system utilizes a similar organizational scheme to facilitate odor detection. Curiously, olfactory sensory neurons (OSNs) in the mouse nose are differentially stimulated depending on the cell location. We therefore asked whether OSNs in different locations evolve unique structural and/or functional features to optimize odor detection and discrimination. Using immunohistochemistry, computational fluid dynamics modeling, and patch clamp recording, we discovered that OSNs situated in highly stimulated regions have much longer cilia and are more sensitive to odorants than those in weakly stimulated regions. Surprisingly, reduction in neuronal excitability or ablation of the olfactory G protein in OSNs does not alter the cilia length pattern, indicating that neither spontaneous nor odor-evoked activity is required for its establishment. Furthermore, the pattern is evident at birth, maintained into adulthood, and restored following pharmacologically induced degeneration of the olfactory epithelium, suggesting that it is intrinsically programmed. Intriguingly, type III adenylyl cyclase (ACIII), a key protein in olfactory signal transduction and ubiquitous marker for primary cilia, exhibits location-dependent gene expression levels, and genetic ablation of ACIII dramatically alters the cilia pattern. These findings reveal an intrinsically programmed configuration in the nose to ensure high sensitivity to odors.

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Section: Resultsmentioning

confidence: 99%

An Olfactory Cilia Pattern in the Mammalian Nose Ensures High Sensitivity to Odors

et al. 2015

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“…Signaling pathways known to be involved with dynamic control of cilium length include cAMP-dependent protein kinase A (PKA) activation [34, 35] and ros cross-hybridizing kinases (RCKs) [36]. While measurements of cilium lengths are subject to fixation errors [37] as many fixatives grossly deform cilia morphology, few reports of measured cilium lengths using live cilia exist.…”

Section: Resultsmentioning

confidence: 99%

HIF Stabilization Weakens Primary Cilia

Resnick

2016

PLoS ONE

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Although solitary or sensory cilia are present in most cells of the body and their existence has been known since the sixties, very little is known about their functions. One suspected function is fluid flow sensing- physical bending of cilia produces an influx of Ca++, which can then result in a variety of activated signaling pathways. Defective cilia and ciliary-associated proteins have been shown to result in cystic diseases. Autosomal Dominant Polycystic Kidney Disease (ADPKD) is a progressive disease, typically appearing in the 5th decade of life and is one of the most common monogenetic inherited human diseases, affecting approximately 600,000 people in the United States. Because the mechanical properties of cilia impact their response to applied flow, we asked how the stiffness of cilia can be controlled pharmacologically. We performed an experiment subjecting cilia to Taxol (a microtubule stabilizer) and CoCl2 (a HIF stabilizer to model hypoxia). Madin-Darby Canine Kidney (MDCK) cells were selected as our model system. After incubation with a selected pharmacological agent, cilia were optically trapped and the bending modulus measured. We found that HIF stabilization significantly weakens cilia. These results illustrate a method to alter the mechanical properties of primary cilia and potentially alter the flow sensing properties of cilia.

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“…The best way to identify the optimal length of cilia is by studying the association between the cilium length and function (Nauli et al, 2008). In general, the longer the cilia, the more sensitive they are to being bent and activated by fluid-shear stress (Abdul-Majeed, Moloney, & Nauli, 2012; Abdul-Majeed & Nauli, 2011b). However, long cilia are less stable and can fall off easily, resulting in cells without cilia.…”

Section: Identification Of Primary Ciliummentioning

confidence: 99%

Non-Motile Primary Cilia as Fluid Shear Stress Mechanosensors

Nauli¹,

Jin²,

AbouAlaiwi³

et al. 2013

Methods in Enzymology

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Primary cilia are sensory organelles that transmit extracellular signals into intracellular biochemical responses. Structural and functional defects in primary cilia are associated with a group of human diseases, known as ciliopathies, with phenotypes ranging from cystic kidney and obesity to blindness and mental retardation. Primary cilia mediate mechano- and chemosensation in many cell types. The mechanosensory function of the primary cilia requires the atypical G-protein-coupled receptor polycystin-1 and the calcium-permeable nonselective cation channel polycystin-2. Mechanical stimulations such as fluid-shear stress of the primary cilia initiate intracellular calcium rise, nitric oxide release, and protein modifications. In this review, we describe a set of protocols for cell culture to promote ciliation, mechanical stimulations of the primary cilia, and measurements of calcium rise and nitric oxide release induced by fluid shear stress.

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Mechanisms regulating cilia growth and cilia function in endothelial cells

Cited by 75 publications

References 31 publications

An Olfactory Cilia Pattern in the Mammalian Nose Ensures High Sensitivity to Odors

An Olfactory Cilia Pattern in the Mammalian Nose Ensures High Sensitivity to Odors

HIF Stabilization Weakens Primary Cilia

Non-Motile Primary Cilia as Fluid Shear Stress Mechanosensors

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