Provider: - Institution: - Data provided by Europeana Collections- All metadata published by Europeana are available free of restriction under the Creative Commons CC0 1.0 Universal Public Domain ...Dedication. However, Europeana requests that you actively acknowledge and give attribution to all metadata sources including Europeana
Provider: - Institution: - Data provided by Europeana Collections- All metadata published by Europeana are available free of restriction under the Creative Commons CC0 1.0 Universal Public Domain ...Dedication. However, Europeana requests that you actively acknowledge and give attribution to all metadata sources including Europeana
Huntington disease (HD) is a devastating autosomal-dominant neurodegenerative disorder. It is caused by expansion of a CAG repeat in the first exon of the huntingtin (HTT) gene that encodes a mutant ...HTT protein with a polyglutamine (polyQ) expansion at the amino terminus. Here, we demonstrate that WT HTT regulates ciliogenesis by interacting through huntingtin-associated protein 1 (HAP1) with pericentriolar material 1 protein (PCM1). Loss of Htt in mouse cells impaired the retrograde trafficking of PCM1 and thereby reduced primary cilia formation. In mice, deletion of Htt in ependymal cells led to PCM1 mislocalization, alteration of the cilia layer, and hydrocephalus. Pathogenic polyQ expansion led to centrosomal accumulation of PCM1 and abnormally long primary cilia in mouse striatal cells. PCM1 accumulation in ependymal cells was associated with longer cilia and disorganized cilia layers in a mouse model of HD and in HD patients. Longer cilia resulted in alteration of the cerebrospinal fluid flow. Thus, our data indicate that WT HTT is essential for protein trafficking to the centrosome and normal ciliogenesis. In HD, hypermorphic ciliogenesis may affect signaling and neuroblast migration so as to dysregulate brain homeostasis and exacerbate disease progression.
Primary cilia are sensors of chemical and mechanical signals in the extracellular environment. The formation of primary cilia (i.e. ciliogenesis) requires dynamic membrane trafficking events, and ...several Rab small GTPases, key regulators of membrane trafficking, have recently been reported to participate in ciliogenesis. However, the precise mechanisms of Rab-mediated membrane trafficking during ciliogenesis remain largely unknown. In the present study, we used a collection of siRNAs against 62 human Rabs to perform a comprehensive knockdown screening for Rabs that regulate serum starvation-induced ciliogenesis in human telomerase reverse transcriptase retinal pigment epithelium 1 (hTERT-RPE1) cells and succeeded in identifying Rab34 as an essential Rab. Knockout (KO) of Rab34, but not of Rabs previously reported to regulate ciliogenesis (e.g. Rab8 and Rab10) in hTERT-RPE1 cells, drastically impaired serum starvation-induced ciliogenesis. Rab34 was also required for serum starvation-induced ciliogenesis in NIH/3T3 cells and MCF10A cells but not for ciliogenesis in Madin-Darby canine kidney (MDCK)-II cysts. We then attempted to identify a specific region(s) of Rab34 that is essential for ciliogenesis by performing deletion and mutation analyses of Rab34. Unexpectedly, instead of a specific sequence in the switch II region, which is generally important for recognizing effector proteins (e.g. Rab interacting lysosomal protein RILP), a unique long N-terminal region of Rab34 before the conserved GTPase domain was found to be essential. These findings suggest that Rab34 is an atypical Rab that regulates serum starvation-induced ciliogenesis through its unique N-terminal region.
Tubulin post-translational modifications generate microtubule heterogeneity and modulate microtubule function, and are catalyzed by tubulin tyrosine ligase-like (TTLL) proteins. Using antibodies ...specific to monoglycylated, polyglycylated, and glutamylated tubulin in whole mount immunostaining of zebrafish embryos, we observed distinct, tissue-specific patterns of tubulin modifications. Tubulin modification patterns in cilia correlated with the expression of ttll3 and ttll6 in ciliated cells. Expression screening of all zebrafish tubulin tyrosine ligase-like genes revealed additional tissue-specific expression of ttll1 in brain neurons, ttll4 in muscle, and ttll7 in otic placodes. Knockdown of ttll3 eliminated cilia tubulin glycylation but had surprisingly mild effects on cilia structure and motility. Similarly, knockdown of ttll6 strongly reduced cilia tubulin glutamylation but only partially affected cilia structure and motility. Combined loss of function of ttll3 and ttll6 caused near complete loss of cilia motility and induced a variety of axonemal ultrastructural defects similar to defects previously observed in zebrafish fleer mutants, which were shown to lack tubulin glutamylation. Consistently, we find that fleer mutants also lack tubulin glycylation. These results indicate that tubulin glycylation and glutamylation have overlapping functions in maintaining cilia structure and motility and that the fleer/dyf-1 TPR protein is required for both types of tubulin post-translational modification.
This study aims to report a case of bilateral descemetocele associated with dystichiasis, which received surgical treatment. Bilateral keratoplasty with pedicled conjunctival flap and manual ...epilation. The patient (Shih Tzu dog, 5 years old) was seen at the Doctor Vet clinic (Nucleus of Veterinary Specialties), located in the Commercial Area Local Residencial Norte, Quadra 712, Bloco G, Loja 15 Asa Norte - Brasília DF. The tutor reported that the patient was quieter than usual, with a lot of eye discharge, keeping her eyes always closed and showing a lot of pain when cleaning. In the specific physical examination, the patient was responsive to the threat, when evaluating the eyeball, bilateral dystachiasis (eyelids), presence of greenish secretion in the mucosa of both eyes, hyperemic conjunctiva of both the right and left eyes was observed in the cornea was noted, with the aid of a slit lamp, the right eye with intense and diffuse edema with vessels and descemetocele, already in the left eye, in addition to the same corneal changes of the right eye, showed dorsal bullous keratitis. The fluorescein test was performed for diagnostic purposes. In view of the above, the animal was diagnosed with bilateral descemetocele and dystichiasis. For treatment, keratoplasty and manual epilation were indicated respectively. Keratoplasty using a pedicled conjunctival graft proved to be effective, repairing and preventing the progression of the descemetocele and consequently corneal rupture in both eyes, leaving only a scar on the cornea. However, since it is a patient who presents with cilia disorders, periodic clinical monitoring is essential.
Este trabalho objetiva relatar um caso de descemetocele bilateral associado à distiquíase, o qual recebeu tratamento cirúrgico. Realizou-se ceratoplastia bilateral com retalho conjuntival pediculado e epilação manual. A paciente (cadela da raça Shih Tzu, cinco anos de idade) foi atendida na clínica Doctor Vet (Núcleo de Especialidades Veterinária), localizada no Setor Comercial Local Residencial Norte, Quadra 712, Bloco G, Loja 15 Asa Norte - Brasília DF. A tutora relatou que a paciente, ficou mais quieta que o normal, com muita secreção ocular, mantendo os olhos sempre fechados e apresentando muita dor na hora de limpar. No exame físico específico, a paciente mostrou-se responsiva a ameaça, ao avaliar o bulbo ocular observou-se, distiquíase bilateral (pálpebras), presença de secreção esverdeada na mucosa de ambos os olhos, conjuntiva hiperêmica tanto do olho direito como esquerdo, na córnea notou-se, com o auxílio da lâmpada de fenda, o olho direito com edema intenso e difuso com vasos e descemetocele, já no olho esquerdo, além das mesmas alterações corneanas do olho direito, evidenciou ceratite bolhosa dorsal. O teste de fluoresceína foi realizado para fins diagnóstico. Diante do exposto o animal foi diagnosticado com descemetocele bilateral e distiquíase. Para tratamento foi indicado a ceratoplastia e epilação manual respectivamente. A ceratoplastia utilizando enxerto conjuntival pediculado mostrou-se eficaz, reparando e evitando a progressão da descemetocele e consequentemente ruptura corneal em ambos os olhos, restando apenas uma cicatriz na córnea. No entanto, por se tratar de uma paciente que apresenta distúrbios dos cílios, é fundamental o acompanhamento clínico periódico.
A distiquíase é considerada a alteração de cílios mais comum nos cães, tendo maior predisposição em raças braquicefálicas, em decorrência de sua anatomia. Esta afecção pode ocorrer de forma uni ou ...bilateral, na pálpebra superior e/ou inferior, sendo que, neste estudo, mostrou maior prevalência apenas da pálpebra superior. Caracterizada pela produção de cílios extras na placa tarsal, estes emergem na margem palpebral pelos orifícios livres próximos a glândula de Meibômius e entram em contato direto com a córnea. A córnea é uma área de alta sensibilidade, susceptível às lesões e ulcerações por essas dístiquias, sendo necessário realizar sua remoção. Este estudo, foi realizado com sete cães, de raças distintas, visando apresentar uma abordagem alternativa à epilação mecânica, sendo realizada a remoção dos cílios pela eletrocauterização por laser cirúrgico, mostrando suas vantagens e se esta técnica foi efetiva com relação ao tratamento.
Cilia are microtubule-based structures that project into the extracellular space. Ciliary defects are associated with several human diseases, including polycystic kidney disease, primary ciliary ...dyskinesia, left–right axis patterning, hydrocephalus and retinal degeneration. However, the genetic and cellular biological control of ciliogenesis remains poorly understood. The IFT46 is one of the highly conserved intraflagellar transport complex B proteins. In zebrafish, ift46 is expressed in various ciliated tissues such as Kupffer׳s vesicle, pronephric ducts, ears and spinal cord. We show that ift46 is localized to the basal body. Knockdown of ift46 gene results in multiple phenotypes associated with various ciliopathies including kidney cysts, pericardial edema and ventral axis curvature. In ift46 morphants, cilia in kidney and spinal canal are shortened and abnormal. Similar ciliary defects are observed in otic vesicles, lateral line hair cells, olfactory pits, but not in Kupffer׳s vesicle. To explore the functions of Ift46 during mouse development, we have generated Ift46 knock-out mice. The Ift46 mutants have developmental defects in brain, neural tube and heart. In particular Ift46(−/−) homozygotes displays randomization of the embryo heart looping, which is a hallmark of defective left–right (L/R) axis patterning. Taken together, our results demonstrated that IFT46 has an essential role in vertebrate ciliary development.
•IFT46 over-expression induces apoptosis in developing zebrafish embryos.•Loss of IFT46 displays typical phenotypes of ciliary defects in zebrafish and mice.•IFT46 C-terminal domain is required for IFT46 function.•IFT46 is not essential for axonemal dynein assembly in zebrafish.
PDF
