scholarly journals Current understandings of the relationship between extracellular vesicles and cilia

Author(s):  
Koji Ikegami ◽  
Faryal Ijaz

Abstract Mammalian cells have a tiny hair-like protrusion on their surface called a primary cilium. Primary cilia are thought to be the antennae for the cells, receiving signals from the environment. In some studies, extracellular vesicles (EVs) were found attached to the surface of the primary cilium. An idea for the phenomenon is that the primary cilium is the receptor for receiving the EVs. Meanwhile, a unicellular organism, Chlamydomonas, which has two long cilia, usually called flagella, release EVs termed ectosomes from the surface of the flagella. Accumulating evidence suggests that the primary cilium also functions as the ‘emitter’ of EVs. Physiological and pathological impacts are also elucidated for the release of EVs from primary cilia. However, the roles of released cilia-derived EVs remain to be clarified. This review introduces the historical background of the relationship between EVs and cilia, and recent progresses in the research field.

2021 ◽  
Author(s):  
Shuwei Xie ◽  
Ellie Smith ◽  
Carter Dierlam ◽  
Danita Mathew ◽  
Angelina Davis ◽  
...  

The mammalian retromer is comprised of subunits VPS26, VPS29 and VPS35, and a more loosely-associated sorting nexin (SNX) heterodimer. Despite known roles for the retromer in multiple trafficking events in yeast and mammalian cells, its role in development is poorly understood, and its potential function in primary ciliogenesis remains unknown. Using CRISPR-Cas9 editing, we demonstrated that vps-26 homozygous knockout C. elegans have reduced brood sizes and impaired vulval development, as well as decreased body length which has been linked to defects in primary ciliogenesis. Since many endocytic proteins are implicated in the generation of primary cilia, we addressed whether the retromer regulates ciliogenesis in mammalian cells. We observed VPS35 localized to the primary cilium, and depletion of VPS26, VPS35 or SNX1/SNX5 led to decreased ciliogenesis. Retromer also coimmunoprecipitated with the capping protein, CP110, and was required for its removal from the mother centriole. Herein, we characterize new roles for the retromer in C. elegans development and in the regulation of ciliogenesis in mammalian cells, and suggest a novel role for the retromer in CP110 removal from the mother centriole.


2021 ◽  
Author(s):  
Gonzalo Sanchez ◽  
Tugce Ceren Incedal ◽  
Juan Prada Salcedo ◽  
Paul O'Callaghan ◽  
Santiago Echeverry ◽  
...  

The primary cilium is an organelle present in most adult mammalian cells and is thought of as an antenna for detection of a variety of signals. Here we use intact mouse pancreatic islets of Langerhans to investigate signalling properties of the primary cilium in β-cells. Using cilia-targeted Ca2+ indicators we find that the resting Ca2+ concentration in the cilium is lower than that of the cytosol, and we uncover a Ca2+ extrusion mechanism in the cilium that effectively insulates the cilium from changes in cytosolic Ca2+. Stimuli that give rise to pronounced cytosolic Ca2+ concentration increases, such as glucose- and depolarization-induced Ca2+ influx, and mobilization of Ca2+ from the ER, was accompanied by minor increases in cilia Ca2+ concentrations that were spatially restricted to a small compartment at the base. Conversely, we observe pronounced Ca2+ concentration changes in the primary cilia of islet β-cells that do not propagate into the cytosol and show that paracrine GABA signalling via cilia-localized GABA- B1-receptors is responsible for this Ca2+ signalling. Finally, we demonstrate that the cilia response to GABA involves ligand-dependent transport of GABA-B1 receptors into the cilium.


2001 ◽  
Vol 7 (S2) ◽  
pp. 4-5
Author(s):  
H. A. Praetorius ◽  
K. R. Spring

The primary cilium, a solitary non-motile structure projecting from the centriole of mammalian cells, has been a subject of interest of anatomists since 1898. Surprisingly, the function of the primary cilium in mammalian cells is completely unknown. Virtually all of the epithelial cells of the mammalian kidney, with the exception of the intercalated cells of the collecting duct, express a single primary cilium on their apical (lumenal) surface. These structures were ignored by physiologists until recently when the mechanical properties of the primary cilia of cultured cells of renal origin were measured and it was proposed that they could serve as flow sensors. The proposal stemmed from the observation that flow rates comparable to those observed in renal tubules resulted in a deflection of the cilium of a few microns and that the stiffness of the cilium was commensurate with mechanosensing.The primary cilia of renal tubular cells are generally about 2 - 3 μm long whereas those of cultured renal cells become much longer as the cells age and may extend 50 μm or more into the medium. MDCK cells, a cultured cell line derived from the collecting duct of the canine kidney, exhibit two cell types analogous to the principal and intercalated cells of the collecting duct. MDCK principal cells express a primary cilium that is visible by high-resolution DIC microscopy. About one week after splitting, the primary cilium of MDCK principal cells is about 8 μm long and is well suited for testing the hypothesis that the cilium serves as a mechanosensor of fluid flow.


2017 ◽  
Vol 96 (9) ◽  
pp. 965-974 ◽  
Author(s):  
M. Hampl ◽  
P. Cela ◽  
H.L. Szabo-Rogers ◽  
M. Kunova Bosakova ◽  
H. Dosedelova ◽  
...  

Primary cilium is a solitary organelle that emanates from the surface of most postmitotic mammalian cells and serves as a sensory organelle, transmitting the mechanical and chemical cues to the cell. Primary cilia are key coordinators of various signaling pathways during development and maintenance of tissue homeostasis. The emerging evidence implicates primary cilia function in tooth development. Primary cilia are located in the dental epithelium and mesenchyme at early stages of tooth development and later during cell differentiation and production of hard tissues. The cilia are present when interactions between both the epithelium and mesenchyme are required for normal morphogenesis. As the primary cilium coordinates several signaling pathways essential for odontogenesis, ciliary defects can interrupt the latter process. Genetic or experimental alterations of cilia function lead to various developmental defects, including supernumerary or missing teeth, enamel and dentin hypoplasia, or teeth crowding. Moreover, dental phenotypes are observed in ciliopathies, including Bardet-Biedl syndrome, Ellis-van Creveld syndrome, Weyers acrofacial dysostosis, cranioectodermal dysplasia, and oral-facial-digital syndrome, altogether demonstrating that primary cilia play a critical role in regulation of both the early odontogenesis and later differentiation of hard tissue–producing cells. Here, we summarize the current evidence for the localization of primary cilia in dental tissues and the impact of disrupted cilia signaling on tooth development in ciliopathies.


2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Ann-Kathrin Volz ◽  
Alina Frei ◽  
Viola Kretschmer ◽  
António M. de Jesus Domingues ◽  
Rene F. Ketting ◽  
...  

AbstractPrimary cilia are microtubule based sensory organelles important for receiving and processing cellular signals. Recent studies have shown that cilia also release extracellular vesicles (EVs). Because EVs have been shown to exert various physiological functions, these findings have the potential to alter our understanding of how primary cilia regulate specific signalling pathways. So far the focus has been on lgEVs budding directly from the ciliary membrane. An association between cilia and MVB-derived smEVs has not yet been described. We show that ciliary mutant mammalian cells demonstrate increased secretion of small EVs (smEVs) and a change in EV composition. Characterisation of smEV cargo identified signalling molecules that are differentially loaded upon ciliary dysfunction. Furthermore, we show that these smEVs are biologically active and modulate the WNT response in recipient cells. These results provide us with insights into smEV-dependent ciliary signalling mechanisms which might underly ciliopathy disease pathogenesis.


2017 ◽  
Vol 45 (6) ◽  
pp. 1029-1042 ◽  
Author(s):  
Na Zhang ◽  
Jian Zhang ◽  
Jing Wang

To expand the business ethics research field, and to increase society's understanding of Chinese insurance agents' business ethics, we investigated how gender differences are related to agents' business ethical sensitivity and whether or not these relationships are moderated by empathy. Through a regression analysis of the factors associated with the business ethical sensitivity of 417 Chinese insurance agents, we found that gender played an important role in affecting business ethical sensitivity, and empathy significantly affected business ethical sensitivity. Furthermore, empathy had a moderating effect on the relationship between gender and business ethical sensitivity. Both men and women with strong empathy scored high on business ethical sensitivity; however, men with strong empathy had higher levels of business ethical sensitivity than did women with little empathy. The findings add to the literature by providing insight into the mechanisms responsible for the benefits of empathy in increasing business ethical sensitivity.


2010 ◽  
Vol 432 (1) ◽  
pp. 77-87 ◽  
Author(s):  
Joanne Durgan ◽  
Peter J. Parker

Fbw7 (F-box WD40 protein 7) is a major tumour suppressor, which mediates the degradation of several potent oncogenes. PKC (protein kinase C) comprises a serine/threonine kinase family that can promote transformation when dysregulated. In the present study, we investigated the relationship between Fbw7 and PKC. Multiple members of the PKC superfamily interact with the substrate-binding domain of Fbw7. However, we find no evidence for Fbw7-mediated degradation of PKC. Instead, we demonstrate that Fbw7 is a novel substrate for PKC. Two residues within the isoform-specific N-terminus of Fbw7α are phosphorylated in a PKC-dependent manner, both in vitro and in mammalian cells (Ser10 and Ser18). Mutational analyses reveal that phosphorylation of Fbw7α at Ser10 can regulate its nuclear localization. Cancer-associated mutations in nearby residues (K11R and the addition of a proline residue at position 16) influence Fbw7α localization in a comparable manner, suggesting that mislocalization of this protein may be of pathological significance. Together these results provide evidence for both physical and functional interactions between the PKC and Fbw7 families, and yield insights into the isoform-specific regulation of Fbw7α.


IMP Journal ◽  
2016 ◽  
Vol 10 (3) ◽  
pp. 512-539 ◽  
Author(s):  
Luitzen De Boer ◽  
Poul Houman Andersen

Purpose The purpose of the paper is to contribute to further advancing of IMP as a research field by setting up and starting a theoretical conversation between system theory and the IMP. Design/methodology/approach The approach is based on a narrative literature study and conceptual research. Findings The authors find that system theory and cybernetics can be regarded as important sources of inspiration for early IMP research. The authors identify three specific theoretical “puzzles” in system theory that may serve as useful topics for discussion between system theorists and IMP researchers. Originality/value Only a handful of papers have touched upon the relationship between system theory and IMP before. This paper combines a narrative, historical analysis of this relationship with developing specific suggestions for using system theory as a vehicle for further advancement of IMP research.


ARCHALP ◽  
2020 ◽  
Author(s):  
Antonio De Rossi

"Why the need, in some way the urgency, of a historically retrospective number of «ArchAlp» magazine dedicated to the houses of Alpine modernity? The intent of this issue is to investigate the relationship between twentieth century modernity and contemporaneity in terms of breaks and novelties, of continuity and discontinuity, of shooting, variations and implementations, not just under the formal and linguistic aspect. In other words, are there points of interaction, long lasting red threads between the architectural vision of Lois Welzenbacher, Charlotte Perriand, Carlo Mollino, and that of Peter Zumthor, Gion A. Caminada, Bernardo Bader? It is basically a way to understand the existence of more or less long trajectories in the way architecture has set the critical and cultural field of mountain construction, recognizing differences and specificities. Although these are generally well-known projects, the works published in this issue of «ArchAlp» are not uniformly known in the territories that refer to the Alpine space. Hence the importance of gathering together a series of architectures that have had the potential for prototypes in order to submit them to a general and comparative view. Even in the absence of perhaps direct subsidiaries, the architectures presented in these pages represent an extraordinary patrimony of design moves and strategies which, through the internalization of experiences, deeply influenced the formation and determination of the contemporary architectural research field in the Alpine environment."


Author(s):  
Marco Cancino

Abstract Research addressing the effect of interest on learning has been thoroughly discussed in learning theory (Renninger et al., 2014). From this rich research field, topic interest has been put forward as a relevant variable in learning in general (Hidi, 2001; Renninger, 2009), and in L2 reading comprehension (Brantmeier, 2006; Eidswick, 2009). However, research focusing on the extent of its influence on L2 incidental vocabulary learning has been scarce (Lee & Pulido, 2017). Thus, this study sought to explore the relationship between topic interest and L2 vocabulary learning by asking 55 male EFL learners at a technological university in Chile to read texts in two conditions (high topic interest and low topic interest) and then assessing incidental learning and retention of twenty target words. Results suggest that topic interest influenced the vocabulary gains made by learners, and that the relationship between topic interest and vocabulary learning and retention can be mediated by dictionary look-up behaviour. Findings are discussed with a focus on the pedagogical actions that can increase learner topic interest.


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