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Cells
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Cilia-Mediated Signaling Pathways
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Cilia-Mediated Signaling Pathways

A special issue of Cells (ISSN 2073-4409). This special issue belongs to the section "Cell Signaling".

Deadline for manuscript submissions: closed (31 March 2024) | Viewed by 4738

Special Issue Editors

Dr. Kirk Mykytyn

E-Mail Website
Guest Editor
Department of Biological Chemistry and Pharmacology, The Ohio State University, Columbus, OH, USA
Interests: neuronal cilia; ependymal cilia; bardet-biedl syndrome; ciliary G protein-coupled receptors; ciliary protein trafficking; ciliopathies; signaling
Dr. Nicolas Berbari

E-Mail Website
Guest Editor
Department of Biology, Indiana University-Purdue University Indianapolis, Indianapolis, IN, USA
Interests: cilia in the CNS; ciliopathy associated obesity; ciliary G protein-coupled receptors; hedgehog signaling

Special Issue Information

Dear Colleagues,

Cilia are evolutionarily conserved organelles that extend from cells to provide critical sensory, signaling, and motility properties. Cilia are restricted compartments, and their functions are defined by the proteins that are targeted to and enriched in the ciliary membrane and cytosol. Numerous signaling pathways are mediated by cilia in response to diverse external signals, such as photons, peptides, chemicals, protons, and lipids. Cilia-mediated signaling is critical for proper cellular function, and in humans, defects in ciliary signaling are associated with many genetic diseases, collectively termed ciliopathies, that impact a wide range of organ systems. 

This Special Issue invites original research and review papers that focus on cilia-based signaling pathways. The scope is broad, and papers can cover ciliary signaling pathways in diverse model organisms (unicellular, invertebrate, or vertebrate) and systems (tissues or cell culture), irrespective of the functional output.

Dr. Kirk Mykytyn
Dr. Nicolas Berbari
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Cells is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2700 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • primary cilia
  • motile cilia
  • ciliary signaling
  • ciliopathy
  • development
  • cellular homeostasis
  • unicellular organism
  • invertebrate and vertebrate models
  • cell/tissue culture

Published Papers (3 papers)

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Research

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18 pages, 13331 KiB  
Article
Postnatal Dynamic Ciliary ARL13B and ADCY3 Localization in the Mouse Brain
by Katlyn K. Brewer, Kathryn M. Brewer, Tiffany T. Terry, Tamara Caspary, Christian Vaisse and Nicolas F. Berbari
Cells 2024, 13(3), 259; https://doi.org/10.3390/cells13030259 - 30 Jan 2024
Viewed by 1390
Abstract
Primary cilia are hair-like structures found on nearly all mammalian cell types, including cells in the developing and adult brain. A diverse set of receptors and signaling proteins localize within cilia to regulate many physiological and developmental pathways, including the Hedgehog (Hh) pathway. [...] Read more.
Primary cilia are hair-like structures found on nearly all mammalian cell types, including cells in the developing and adult brain. A diverse set of receptors and signaling proteins localize within cilia to regulate many physiological and developmental pathways, including the Hedgehog (Hh) pathway. Defects in cilia structure, protein localization, and function lead to genetic disorders called ciliopathies, which present with various clinical features that include several neurodevelopmental phenotypes and hyperphagia-associated obesity. Despite their dysfunction being implicated in several disease states, understanding their roles in central nervous system (CNS) development and signaling has proven challenging. We hypothesize that dynamic changes to ciliary protein composition contribute to this challenge and may reflect unrecognized diversity of CNS cilia. The proteins ARL13B and ADCY3 are established markers of cilia in the brain. ARL13B is a regulatory GTPase important for regulating cilia structure, protein trafficking, and Hh signaling, and ADCY3 is a ciliary adenylyl cyclase. Here, we examine the ciliary localization of ARL13B and ADCY3 in the perinatal and adult mouse brain. We define changes in the proportion of cilia enriched for ARL13B and ADCY3 depending on brain region and age. Furthermore, we identify distinct lengths of cilia within specific brain regions of male and female mice. ARL13B+ cilia become relatively rare with age in many brain regions, including the hypothalamic feeding centers, while ADCY3 becomes a prominent cilia marker in the mature adult brain. It is important to understand the endogenous localization patterns of these proteins throughout development and under different physiological conditions as these common cilia markers may be more dynamic than initially expected. Understanding regional- and developmental-associated cilia protein composition signatures and physiological condition cilia dynamic changes in the CNS may reveal the molecular mechanisms associated with the features commonly observed in ciliopathy models and ciliopathies, like obesity and diabetes. Full article
(This article belongs to the Special Issue Cilia-Mediated Signaling Pathways)
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20 pages, 5870 KiB  
Article
Increasing Ciliary ARL13B Expression Drives Active and Inhibitor-Resistant Smoothened and GLI into Glioma Primary Cilia
by Ping Shi, Jia Tian, Julianne C. Mallinger, Dahao Ling, Loic P. Deleyrolle, Jeremy C. McIntyre, Tamara Caspary, Joshua J. Breunig and Matthew R. Sarkisian
Cells 2023, 12(19), 2354; https://doi.org/10.3390/cells12192354 - 26 Sep 2023
Cited by 2 | Viewed by 1858
Abstract
ADP-ribosylation factor-like protein 13B (ARL13B), a regulatory GTPase and guanine exchange factor (GEF), enriches in primary cilia and promotes tumorigenesis in part by regulating Smoothened (SMO), GLI, and Sonic Hedgehog (SHH) signaling. Gliomas with increased ARL13B, SMO, and GLI2 expression are [...] Read more.
ADP-ribosylation factor-like protein 13B (ARL13B), a regulatory GTPase and guanine exchange factor (GEF), enriches in primary cilia and promotes tumorigenesis in part by regulating Smoothened (SMO), GLI, and Sonic Hedgehog (SHH) signaling. Gliomas with increased ARL13B, SMO, and GLI2 expression are more aggressive, but the relationship to cilia is unclear. Previous studies have showed that increasing ARL13B in glioblastoma cells promoted ciliary SMO accumulation, independent of exogenous SHH addition. Here, we show that SMO accumulation is due to increased ciliary, but not extraciliary, ARL13B. Increasing ARL13B expression promotes the accumulation of both activated SMO and GLI2 in glioma cilia. ARL13B-driven increases in ciliary SMO and GLI2 are resistant to SMO inhibitors, GDC-0449, and cyclopamine. Surprisingly, ARL13B-induced changes in ciliary SMO/GLI2 did not correlate with canonical changes in downstream SHH pathway genes. However, glioma cell lines whose cilia overexpress WT but not guanine exchange factor-deficient ARL13B, display reduced INPP5e, a ciliary membrane component whose depletion may favor SMO/GLI2 enrichment. Glioma cells overexpressing ARL13B also display reduced ciliary intraflagellar transport 88 (IFT88), suggesting that altered retrograde transport could further promote SMO/GLI accumulation. Collectively, our data suggest that factors increasing ARL13B expression in glioma cells may promote both changes in ciliary membrane characteristics and IFT proteins, leading to the accumulation of drug-resistant SMO and GLI. The downstream targets and consequences of these ciliary changes require further investigation. Full article
(This article belongs to the Special Issue Cilia-Mediated Signaling Pathways)
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Review

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18 pages, 4058 KiB  
Review
Cilia Provide a Platform for the Generation, Regulated Secretion, and Reception of Peptidergic Signals
by Raj Luxmi and Stephen M. King
Cells 2024, 13(4), 303; https://doi.org/10.3390/cells13040303 - 6 Feb 2024
Viewed by 1031
Abstract
Cilia are microtubule-based cellular projections that act as motile, sensory, and secretory organelles. These structures receive information from the environment and transmit downstream signals to the cell body. Cilia also release vesicular ectosomes that bud from the ciliary membrane and carry an array [...] Read more.
Cilia are microtubule-based cellular projections that act as motile, sensory, and secretory organelles. These structures receive information from the environment and transmit downstream signals to the cell body. Cilia also release vesicular ectosomes that bud from the ciliary membrane and carry an array of bioactive enzymes and peptide products. Peptidergic signals represent an ancient mode of intercellular communication, and in metazoans are involved in the maintenance of cellular homeostasis and various other physiological processes and responses. Numerous peptide receptors, subtilisin-like proteases, the peptide-amidating enzyme, and bioactive amidated peptide products have been localized to these organelles. In this review, we detail how cilia serve as specialized signaling organelles and act as a platform for the regulated processing and secretion of peptidergic signals. We especially focus on the processing and trafficking pathways by which a peptide precursor from the green alga Chlamydomonas reinhardtii is converted into an amidated bioactive product—a chemotactic modulator—and released from cilia in ectosomes. Biochemical dissection of this complex ciliary secretory pathway provides a paradigm for understanding cilia-based peptidergic signaling in mammals and other eukaryotes. Full article
(This article belongs to the Special Issue Cilia-Mediated Signaling Pathways)
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