Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 13.360
Filtrar
1.
J Cell Sci ; 136(5)2023 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-35403186

RESUMO

Primary cilia are microtubule-based sensory organelles whose assembly and function rely on the conserved bidirectional intraflagellar transport (IFT) system, which is powered by anterograde kinesin-2 and retrograde cytoplasmic dynein-2 motors. Nematodes additionally employ a cell-type-specific kinesin-3 motor, KLP-6, which moves within cilia independently of IFT and regulates ciliary content and function. Here, we provide evidence that a KLP-6 homolog, KIF13B, undergoes bursts of bidirectional movement within primary cilia of cultured immortalized human retinal pigment epithelial (hTERT-RPE1) cells. Anterograde and retrograde intraciliary velocities of KIF13B were similar to those of IFT (as assayed using IFT172-eGFP), but intraciliary movement of KIF13B required its own motor domain and appeared to be cell-type specific. Our work provides the first demonstration of motor-driven, intraciliary movement by a vertebrate kinesin other than kinesin-2 motors.


Assuntos
Cílios , Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Transporte Biológico , Cílios/metabolismo , Proteínas do Citoesqueleto/metabolismo , Flagelos/metabolismo , Humanos , Microtúbulos
2.
J Cell Sci ; 136(5)2023 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-35531639

RESUMO

Most motile cilia have a stereotyped structure of nine microtubule outer doublets and a single central pair of microtubules. The central pair of microtubules are surrounded by a set of proteins, termed the central pair apparatus. A specific kinesin, Klp1 projects from the central pair and contributes to ciliary motility in Chlamydomonas. The vertebrate ortholog, Kif9, is required for beating in mouse sperm flagella, but the mechanism of Kif9/Klp1 function remains poorly defined. Here, using Xenopus epidermal multiciliated cells, we show that Kif9 is necessary for ciliary motility and the proper distal localization of not only central pair proteins, but also radial spokes and dynein arms. In addition, single-molecule assays in vitro reveal that Xenopus Kif9 is a long-range processive motor, although it does not mediate long-range movement in ciliary axonemes in vivo. Together, our data suggest that Kif9 is integral for ciliary beating and is necessary for proper axonemal distal end integrity.


Assuntos
Axonema , Cílios , Animais , Axonema/metabolismo , Cílios/metabolismo , Dineínas/metabolismo , Flagelos/metabolismo , Microtúbulos/metabolismo , Xenopus
3.
J Cell Biol ; 221(7)2022 Jul 04.
Artigo em Inglês | MEDLINE | ID: mdl-35695891

RESUMO

Wang et al. report in this issue (2022. J. Cell Biol.https://doi.org/10.1083/jcb.202108015) that the SARS-CoV-2 protein ORF10 increases the activity of the E3 ligase CUL2ZYG11B, leading to the degradation of multiple ciliary proteins. The resulting loss of cilia may facilitate the spread of SARS-CoV-2 in the respiratory tree.


Assuntos
COVID-19 , Cílios , Ubiquitina-Proteína Ligases , COVID-19/patologia , Proteínas de Ciclo Celular , Cílios/patologia , Proteínas Culina , Genes Virais , Humanos , Proteínas/metabolismo , SARS-CoV-2 , Ubiquitina-Proteína Ligases/metabolismo
4.
Proc Natl Acad Sci U S A ; 119(24): e2103615119, 2022 Jun 14.
Artigo em Inglês | MEDLINE | ID: mdl-35671424

RESUMO

Skeletal muscle atrophy is commonly associated with aging, immobilization, muscle unloading, and congenital myopathies. Generation of mature muscle cells from skeletal muscle satellite cells (SCs) is pivotal in repairing muscle tissue. Exercise therapy promotes muscle hypertrophy and strength. Primary cilium is implicated as the mechanical sensor in some mammalian cells, but its role in skeletal muscle cells remains vague. To determine mechanical sensors for exercise-induced muscle hypertrophy, we established three SC-specific cilium dysfunctional mouse models-Myogenic factor 5 (Myf5)-Arf-like Protein 3 (Arl3)-/-, Paired box protein Pax-7 (Pax7)-Intraflagellar transport protein 88 homolog (Ift88)-/-, and Pax7-Arl3-/--by specifically deleting a ciliary protein ARL3 in MYF5-expressing SCs, or IFT88 in PAX7-expressing SCs, or ARL3 in PAX7-expressing SCs, respectively. We show that the Myf5-Arl3-/- mice develop grossly the same as WT mice. Intriguingly, mechanical stimulation-induced muscle hypertrophy or myoblast differentiation is abrogated in Myf5-Arl3-/- and Pax7-Arl3-/- mice or primary isolated Myf5-Arl3-/- and Pax7-Ift88-/- myoblasts, likely due to defective cilia-mediated Hedgehog (Hh) signaling. Collectively, we demonstrate SC cilia serve as mechanical sensors and promote exercise-induced muscle hypertrophy via Hh signaling pathway.


Assuntos
Cílios , Força Muscular , Condicionamento Físico Animal , Células Satélites de Músculo Esquelético , Animais , Diferenciação Celular , Cílios/fisiologia , Terapia por Exercício , Proteínas Hedgehog/genética , Proteínas Hedgehog/metabolismo , Camundongos , Fibras Musculares Esqueléticas/citologia , Fibras Musculares Esqueléticas/fisiologia , Fator de Transcrição PAX7/genética , Fator de Transcrição PAX7/metabolismo , Células Satélites de Músculo Esquelético/citologia , Células Satélites de Músculo Esquelético/fisiologia
5.
Physiol Rep ; 10(11): e15349, 2022 06.
Artigo em Inglês | MEDLINE | ID: mdl-35678028

RESUMO

Motile cilia are found in numerous locations throughout our body and play a critical role in various physiological processes. The most commonly used method to assess cilia motility is to quantify cilia beat frequency (CBF) via video microscopy. However, a large heterogeneity exists within published literature regarding the framerate used to image cilia motility for calculating CBF. The aim of this study was to determine the optimal frame rate required to image cilia motility for CBF assessment, and if the Nyquist theorem may be used to set this rate. One-second movies of cilia were collected at >600 fps from mouse airways and ependyma at room-temperature or 37°C. Movies were then down-sampled to 30-300 fps. CBF was quantified for identical cilia at different framerates by either manual counting or automated MATLAB script. Airway CBF was significantly impaired in 30 fps movies, while ependymal CBF was significantly impaired in both 60 and 30 fps movies. Pairwise comparison showed that video framerate should be at least 150 fps to accurately measure CBF, with minimal improvement in CBF accuracy in movies >150 fps. The automated script was also found to be less accurate for measuring CBF in lower fps movies than manual counting, however, this difference disappeared in higher framerate movies (>150 fps). In conclusion, our data suggest the Nyquist theorem is unreliable for setting sampling rate for CBF measurement. Instead, sampling rate should be 3-4 times faster than CBF for accurate CBF assessment. Especially if CBF calculation is to be automated.


Assuntos
Cílios , Sistema Respiratório , Animais , Cílios/fisiologia , Camundongos , Microscopia de Vídeo
6.
Cells ; 11(12)2022 06 09.
Artigo em Inglês | MEDLINE | ID: mdl-35741008

RESUMO

Primary cilia are crucial for normal cardiac organogenesis via the formation of cyto-architectural, anatomical, and physiological boundaries in the developing heart and outflow tract. These tiny, plasma membrane-bound organelles function in a sensory-integrative capacity, interpreting both the intra- and extra-cellular environments and directing changes in gene expression responses to promote, prevent, and modify cellular proliferation and differentiation. One distinct feature of this organelle is its involvement in the propagation of a variety of signaling cascades, most notably, the Hedgehog cascade. Three ligands, Sonic, Indian, and Desert hedgehog, function as growth factors that are most commonly dependent on the presence of intact primary cilia, where the Hedgehog receptors Patched-1 and Smoothened localize directly within or at the base of the ciliary axoneme. Hedgehog signaling functions to mediate many cell behaviors that are critical for normal embryonic tissue/organ development. However, inappropriate activation and/or upregulation of Hedgehog signaling in postnatal and adult tissue is known to initiate oncogenesis, as well as the pathogenesis of other diseases. The focus of this review is to provide an overview describing the role of Hedgehog signaling and its dependence upon the primary cilium in the cell types that are most essential for mammalian heart development. We outline the breadth of developmental defects and the consequential pathologies resulting from inappropriate changes to Hedgehog signaling, as it pertains to congenital heart disease and general cardiac pathophysiology.


Assuntos
Cílios , Proteínas Hedgehog , Animais , Cílios/metabolismo , Coração , Proteínas Hedgehog/metabolismo , Mamíferos/metabolismo , Organogênese , Transdução de Sinais/fisiologia
7.
J Cell Physiol ; 237(6): 2611-2612, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35731937
8.
Cells ; 11(11)2022 06 03.
Artigo em Inglês | MEDLINE | ID: mdl-35681527

RESUMO

The GLI-Similar 1-3 (GLIS1-3) genes, in addition to encoding GLIS1-3 Krüppel-like zinc finger transcription factors, also generate circular GLIS (circGLIS) RNAs. GLIS1-3 regulate gene transcription by binding to GLIS binding sites in target genes, whereas circGLIS RNAs largely act as miRNA sponges. GLIS1-3 play a critical role in the regulation of many biological processes and have been implicated in various pathologies. GLIS protein activities appear to be regulated by primary cilium-dependent and -independent signaling pathways that via post-translational modifications may cause changes in the subcellular localization, proteolytic processing, and protein interactions. These modifications can affect the transcriptional activity of GLIS proteins and, consequently, the biological functions they regulate as well as their roles in disease. Recent studies have implicated GLIS1-3 proteins and circGLIS RNAs in the regulation of stemness, self-renewal, epithelial-mesenchymal transition (EMT), cell reprogramming, lineage determination, and differentiation. These biological processes are interconnected and play a critical role in embryonic development, tissue homeostasis, and cell plasticity. Dysregulation of these processes are part of many pathologies. This review provides an update on our current knowledge of the roles GLIS proteins and circGLIS RNAs in the control of these biological processes in relation to their regulation of normal physiological functions and disease.


Assuntos
Autorrenovação Celular , Fatores de Transcrição , Cílios/metabolismo , Fatores de Transcrição Kruppel-Like/metabolismo , Fatores de Transcrição/metabolismo , Dedos de Zinco/genética
9.
J Cell Sci ; 135(12)2022 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-35673984

RESUMO

The kinesin-3 motor KIF13B functions in endocytosis, vesicle transport and regulation of ciliary length and signaling. Direct binding of the membrane-associated guanylate kinase (MAGUK) DLG1 to the MAGUK-binding stalk domain of KIF13B relieves motor autoinhibition and promotes microtubule plus-end-directed cargo transport. Here, we characterize angiomotin (AMOT) isoform 2 (p80, referred to as Ap80) as a novel KIF13B interactor that promotes binding of another MAGUK, the polarity protein and Crumbs complex component PALS1, to KIF13B. Live-cell imaging analysis indicated that Ap80 is concentrated at and recruits PALS1 to the base of the primary cilium, but is not a cargo of KIF13B itself. Consistent with a ciliary function for Ap80, its depletion led to elongated primary cilia and reduced agonist-induced ciliary accumulation of SMO, a key component of the Hedgehog signaling pathway, whereas Ap80 overexpression caused ciliary shortening. Our results suggest that Ap80 activates KIF13B cargo binding at the base of the primary cilium to regulate ciliary length, composition and signaling.


Assuntos
Proteínas de Membrana , Cílios/metabolismo , Guanilato Quinases , Proteínas Hedgehog/metabolismo , Proteínas de Membrana/metabolismo , Isoformas de Proteínas
10.
PLoS Genet ; 18(6): e1009896, 2022 06.
Artigo em Inglês | MEDLINE | ID: mdl-35653384

RESUMO

CCDC28B (coiled-coil domain-containing protein 28B) was identified as a modifier in the ciliopathy Bardet-Biedl syndrome (BBS). Our previous work in cells and zebrafish showed that CCDC28B plays a role regulating cilia length in a mechanism that is not completely understood. Here we report the generation of a Ccdc28b mutant mouse using CRISPR/Cas9 (Ccdc28b mut). Depletion of CCDC28B resulted in a mild phenotype. Ccdc28b mut animals i) do not present clear structural cilia affectation, although we did observe mild defects in cilia density and cilia length in some tissues, ii) reproduce normally, and iii) do not develop retinal degeneration or obesity, two hallmark features of reported BBS murine models. In contrast, Ccdc28b mut mice did show clear social interaction defects as well as stereotypical behaviors. This finding is indeed relevant regarding CCDC28B as a modifier of BBS since behavioral phenotypes have been documented in BBS. Overall, this work reports a novel mouse model that will be key to continue evaluating genetic interactions in BBS, deciphering the contribution of CCDC28B to modulate the presentation of BBS phenotypes. In addition, our data underscores a novel link between CCDC28B and behavioral defects, providing a novel opportunity to further our understanding of the genetic, cellular, and molecular basis of these complex phenotypes.


Assuntos
Síndrome de Bardet-Biedl , Degeneração Retiniana , Animais , Síndrome de Bardet-Biedl/genética , Síndrome de Bardet-Biedl/metabolismo , Cílios/metabolismo , Camundongos , Fenótipo , Degeneração Retiniana/genética , Peixe-Zebra/genética
11.
J Cell Physiol ; 237(6): 2613-2631, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35661356

RESUMO

Cilium, a tiny microtubule-based cellular appendage critical for cell signalling and physiology, displays a large variety of receptors. The composition and turnover of ciliary lipids and receptors determine cell behaviour. Due to the exclusion of ribosomal machinery and limited membrane area, a cilium needs adaptive logistics to actively reconstitute the lipid and receptor compositions during development and differentiation. How is this dynamicity generated? Here, we examine whether, along with the Intraflagellar-Transport, targeted changes in sector-wise lipid composition could control the receptor localisation and functions in the cilia. We discuss how an interplay between ciliary lipid composition, localised lipid modification, and receptor function could contribute to cilia growth and signalling. We argue that lipid modification at the cell-cilium interface could generate an added thrust for a selective exchange of membrane lipids and the transmembrane and membrane-associated proteins.


Assuntos
Cílios , Proteínas de Membrana , Transporte Biológico , Cílios/metabolismo , Lipídeos de Membrana/metabolismo , Proteínas de Membrana/metabolismo , Microtúbulos/metabolismo
12.
Biomolecules ; 12(6)2022 Jun 17.
Artigo em Inglês | MEDLINE | ID: mdl-35740972

RESUMO

Primary cilia are non-motile organelles associated with the cell cycle, which can be found in most vertebrate cell types. Cilia formation occurs through a process called ciliogenesis, which involves several mechanisms including planar cell polarity (PCP) and the Hedgehog (Hh) signaling pathway. Some gene complexes, such as BBSome or CPLANE (ciliogenesis and planar polarity effector), have been linked to ciliogenesis. CPLANE complex is composed of INTU, FUZ and WDPCP, which bind to JBTS17 and RSG1 for cilia formation. Defects in these genes have been linked to a malfunction of intraflagellar transport and defects in the planar cell polarity, as well as defective activation of the Hedgehog signalling pathway. These faults lead to defective cilium formation, resulting in ciliopathies, including orofacial-digital syndrome (OFDS) and Bardet-Biedl syndrome (BBS). Considering the close relationship, between the CPLANE complex and cilium formation, it can be expected that defects in the genes that encode subunits of the CPLANE complex may be related to other ciliopathies.


Assuntos
Ciliopatias , Proteínas Hedgehog , Polaridade Celular/genética , Cílios/genética , Cílios/metabolismo , Ciliopatias/genética , Ciliopatias/metabolismo , Proteínas Hedgehog/genética , Proteínas Hedgehog/metabolismo , Humanos , Transporte Proteico/genética
13.
Development ; 149(12)2022 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-35708608

RESUMO

Motile cilia generate cell propulsion and extracellular fluid flows that are crucial for airway clearance, fertility and left-right patterning. Motility is powered by dynein arm complexes that are assembled in the cytoplasm then imported into the cilium. Studies in Chlamydomonas reinhardtii showed that ODA16 is a cofactor which promotes dynein arm import. Here, we demonstrate that the zebrafish homolog of ODA16, Daw1, facilitates the onset of robust cilia motility during development. Without Daw1, cilia showed markedly reduced motility during early development; however, motility subsequently increased to attain close to wild-type levels. Delayed motility onset led to differential effects on early and late cilia-dependent processes. Remarkably, abnormal body axis curves, which formed during the first day of development due to reduced cilia motility, self-corrected when motility later reached wild-type levels. Zebrafish larva therefore possess the ability to survey and correct body shape abnormalities. This work defines Daw1 as a factor which promotes the onset of timely cilia motility and can explain why human patients harboring DAW1 mutations exhibit significant laterality perturbations but mild airway and fertility complications.


Assuntos
Cílios , Dineínas , Animais , Movimento Celular , Cílios/metabolismo , Dineínas/metabolismo , Humanos , Mutação/genética , Peixe-Zebra/genética , Peixe-Zebra/metabolismo , Proteínas de Peixe-Zebra/genética , Proteínas de Peixe-Zebra/metabolismo
14.
PLoS Biol ; 20(6): e3001649, 2022 06.
Artigo em Inglês | MEDLINE | ID: mdl-35709082

RESUMO

Inherited retinal degeneration due to loss of photoreceptor cells is a leading cause of human blindness. These cells possess a photosensitive outer segment linked to the cell body through the connecting cilium (CC). While structural defects of the CC have been associated with retinal degeneration, its nanoscale molecular composition, assembly, and function are barely known. Here, using expansion microscopy and electron microscopy, we reveal the molecular architecture of the CC and demonstrate that microtubules are linked together by a CC inner scaffold containing POC5, CENTRIN, and FAM161A. Dissecting CC inner scaffold assembly during photoreceptor development in mouse revealed that it acts as a structural zipper, progressively bridging microtubule doublets and straightening the CC. Furthermore, we show that Fam161a disruption in mouse leads to specific CC inner scaffold loss and triggers microtubule doublet spreading, prior to outer segment collapse and photoreceptor degeneration, suggesting a molecular mechanism for a subtype of retinitis pigmentosa.


Assuntos
Degeneração Retiniana , Retinite Pigmentosa , Animais , Cílios , Proteínas do Olho , Camundongos , Microtúbulos
15.
J Neuroinflammation ; 19(1): 156, 2022 Jun 17.
Artigo em Inglês | MEDLINE | ID: mdl-35715859

RESUMO

The choroid plexus is a tissue located in the lateral ventricles of the brain and is composed mainly of choroid plexus epithelium cells. The main function is currently thought to be the secretion of cerebrospinal fluid and the regulation of its pH, and more functions are gradually being demonstrated. Assistance in the removal of metabolic waste and participation in the apoptotic pathway are also the functions of choroid plexus. Besides, it helps to repair the brain by regulating the secretion of neuropeptides and the delivery of drugs. It is involved in the immune response to assist in the clearance of infections in the central nervous system. It is now believed that the choroid plexus is in an inflammatory state after damage to the brain. This state, along with changes in the cilia, is thought to be an abnormal physiological state of the choroid plexus, which in turn leads to abnormal conditions in cerebrospinal fluid and triggers hydrocephalus. This review describes the pathophysiological mechanism of hydrocephalus following choroid plexus epithelium cell abnormalities based on the normal physiological functions of choroid plexus epithelium cells, and analyzes the attempts and future developments of using choroid plexus epithelium cells as a therapeutic target for hydrocephalus.


Assuntos
Plexo Corióideo , Hidrocefalia , Plexo Corióideo/metabolismo , Cílios , Epitélio , Humanos , Hidrocefalia/metabolismo , Ventrículos Laterais
16.
J Cell Biol ; 221(7)2022 Jul 04.
Artigo em Inglês | MEDLINE | ID: mdl-35674692

RESUMO

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causal pathogen of the ongoing global pandemic of coronavirus disease 2019 (COVID-19). Loss of smell and taste are symptoms of COVID-19, and may be related to cilia dysfunction. Here, we found that the SARS-CoV-2 ORF10 increases the overall E3 ligase activity of the CUL2ZYG11B complex by interacting with ZYG11B. Enhanced CUL2ZYG11B activity by ORF10 causes increased ubiquitination and subsequent proteasome-mediated degradation of an intraflagellar transport (IFT) complex B protein, IFT46, thereby impairing both cilia biogenesis and maintenance. Further, we show that exposure of the respiratory tract of hACE2 mice to SARS-CoV-2 or SARS-CoV-2 ORF10 alone results in cilia-dysfunction-related phenotypes, and the ORF10 expression in primary human nasal epithelial cells (HNECs) also caused a rapid loss of the ciliary layer. Our study demonstrates how SARS-CoV-2 ORF10 hijacks CUL2ZYG11B to eliminate IFT46 and leads to cilia dysfunction, thereby offering a powerful etiopathological explanation for how SARS-CoV-2 causes multiple cilia-dysfunction-related symptoms specific to COVID-19.


Assuntos
Cílios , SARS-CoV-2 , Ubiquitina-Proteína Ligases , Animais , Células Cultivadas , Cílios/metabolismo , Cílios/patologia , Proteínas do Citoesqueleto , Células Epiteliais/metabolismo , Células Epiteliais/virologia , Humanos , Camundongos , SARS-CoV-2/patogenicidade , Olfato , Ubiquitina-Proteína Ligases/metabolismo
17.
Phys Rev Lett ; 128(20): 208101, 2022 May 20.
Artigo em Inglês | MEDLINE | ID: mdl-35657856

RESUMO

To rotate continuously without jamming, the flagellar filaments of bacteria need to be locked in phase. While several models have been proposed for eukaryotic flagella, the synchronization of bacterial flagella is less well understood. Starting from a reduced model of flexible and hydrodynamically coupled bacterial flagella, we rigorously coarse grain the equations of motion using the method of multiple scales, and hence show that bacterial flagella generically synchronize to zero phase difference via an elastohydrodynamic mechanism. Remarkably, the far-field rate of synchronization is maximized at an intermediate value of elastic compliance, with surprising implications for bacteria.


Assuntos
Flagelos , Modelos Biológicos , Bactérias , Cílios , Movimento (Física)
18.
Cell Death Dis ; 13(6): 559, 2022 Jun 21.
Artigo em Inglês | MEDLINE | ID: mdl-35729109

RESUMO

Primary cilia dyskinesia (PCD) is a rare genetic disease caused by ciliary structural or functional defects. It causes severe outcomes in patients, including recurrent upper and lower airway infections, progressive lung failure, and randomization of heterotaxy. To date, although 50 genes have been shown to be responsible for PCD, the etiology remains elusive. Meanwhile, owing to the lack of a model mimicking the pathogenesis that can be used as a drug screening platform, thereby slowing the development of related therapies. In the current study, we identified compound mutation of DNAH9 in a patient with PCD with the following clinical features: recurrent respiratory tract infections, low lung function, and ultrastructural defects of the outer dynein arms (ODAs). Bioinformatic analysis, structure simulation assay, and western blot analysis showed that the mutations affected the structure and expression of DNAH9 protein. Dnah9 knock-down (KD) mice recapitulated the patient phenotypes, including low lung function, mucin accumulation, and increased immune cell infiltration. Immunostaining, western blot, and co-immunoprecipitation analyses were performed to clarify that DNAH9 interacted with CCDC114/GAS8 and diminished their protein levels. Furthermore, we constructed an airway organoid of Dnah9 KD mice and discovered that it could mimic the key features of the PCD phenotypes. We then used organoid as a drug screening model to identify mitochondrial-targeting drugs that can partially elevate cilia beating in Dnah9 KD organoid. Collectively, our results demonstrated that Dnah9 KD mice and an organoid model can recapture the clinical features of patients with PCD and provide an excellent drug screening platform for human ciliopathies.


Assuntos
Dineínas do Axonema , Discinesias , Síndrome de Kartagener , Animais , Dineínas do Axonema/genética , Dineínas do Axonema/metabolismo , Cílios/metabolismo , Avaliação Pré-Clínica de Medicamentos , Dineínas/metabolismo , Discinesias/metabolismo , Discinesias/patologia , Humanos , Síndrome de Kartagener/genética , Síndrome de Kartagener/metabolismo , Síndrome de Kartagener/patologia , Camundongos , Mutação/genética , Organoides/metabolismo
19.
J Cell Physiol ; 237(6): 2668-2672, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35686462

RESUMO

Sensory cilia, an ancient organelle, displays a high degree of conservation in its structure and functioning. Sensory cilia also fulfill a wide range of sensory functions, from sensing environmental signals (light, sound, chemicals, and mechanical forces) to interpreting intercellular developmental signals. One way they appear to fulfill these diverse and specialized roles is by adopting a variety of shapes and sizes. We are only beginning to document and appreciate this complexity. Here in this review, using the varied and specialized cilia found on Caenorhabditis elegans sensory neurons, I highlight some of the most obvious examples of this structural diversity and the underlying mechanisms if known. Such structural diversity appears to arise from the modulation of deeply conserved molecular pathways and also from cell- and species-specific mechanisms. Studying these ciliary specializations will thus provide for a comprehensive understanding of ciliary biology and might uncover understudied aspects of ciliary disease biology.


Assuntos
Proteínas de Caenorhabditis elegans , Caenorhabditis elegans , Animais , Cílios , Organelas , Células Receptoras Sensoriais
20.
Dev Cell ; 57(12): 1545-1557.e4, 2022 06 20.
Artigo em Inglês | MEDLINE | ID: mdl-35649417

RESUMO

Bardet-Biedl syndrome (BBS) is a genetic disorder that affects primary cilia. BBSome, a protein complex composed of eight BBS proteins, regulates the structure and function of cilia, and its malfunction causes BBS in humans. Here, we report a cilia-independent function of BBSome. To identify genes that regulate the C. elegans photoreceptor protein LITE-1 in ciliated ASH photosensory neurons, we performed a genetic screen and isolated bbs mutants. Functional analysis revealed that BBSome regulates LITE-1 protein stability independently of cilia. Through another round of genetic screening, we found that this cilia-independent function of BBSome is mediated by DLK-MAPK signaling, which acts downstream of BBSome to control LITE-1 stability via Rab5-mediated endocytosis. BBSome exerts its function by regulating the expression of DLK. BBSome also regulates the expression of LZK, a mammalian DLK in human cells. These studies identify a cilia-independent function of BBSome and uncover DLK as an evolutionarily conserved BBSome effector.


Assuntos
Síndrome de Bardet-Biedl , Cílios , Animais , Síndrome de Bardet-Biedl/genética , Síndrome de Bardet-Biedl/metabolismo , Caenorhabditis elegans/genética , Caenorhabditis elegans/metabolismo , Cílios/metabolismo , Humanos , Mamíferos/metabolismo , Transporte Proteico/genética , Proteínas/metabolismo
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...