Caenorhabditis elegans DYF-2, an Orthologue of Human WDR19, Is a Component of the Intraflagellar Transport Machinery in Sensory Cilia

The intraflagellar transport (IFT) machinery required to build functional cilia consists of a multisubunit complex whose molecular composition, organization, and function are poorly understood. Here, we describe a novel tryptophan-aspartic acid (WD) repeat (WDR) containing IFT protein from Caenorhabditis elegans, DYF-2, that plays a critical role in maintaining the structural and functional integrity of the IFT machinery. We determined the identity of the dyf-2 gene by transgenic rescue of mutant phenotypes and by sequencing of mutant alleles. Loss of DYF-2 function selectively affects the assembly and motility of different IFT components and leads to defects in cilia structure and chemosensation in the nematode. Based on these observations, and the analysis of DYF-2 movement in a Bardet–Biedl syndrome mutant with partially disrupted IFT particles, we conclude that DYF-2 can associate with IFT particle complex B. At the same time, mutations in dyf-2 can interfere with the function of complex A components, suggesting an important role of this protein in the assembly of the IFT particle as a whole. Importantly, the mouse orthologue of DYF-2, WDR19, also localizes to cilia, pointing to an important evolutionarily conserved role for this WDR protein in cilia development and function.

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IFT88 transports Gucy2d, a guanylyl cyclase, to maintain sensory cilia function in Drosophila

10.1101/2020.12.15.417840 ◽

2020 ◽

Author(s):

Sascha Werner ◽

Sihem Zitouni ◽

Pilar Okenve-Ramos ◽

Susana Mendonca ◽

Anje Sporbert ◽

...

Keyword(s):

Drosophila Melanogaster ◽

Guanylyl Cyclase ◽

Potential Role ◽

Late Onset ◽

Intraflagellar Transport ◽

Human Diseases ◽

Evolutionarily Conserved ◽

Sensory Cilia ◽

Ciliated Neurons

Cilia are involved in a plethora of motility and sensory-related functions. Ciliary defects cause several ciliopathies, some of which with late-onset, suggesting cilia are actively maintained. While much is known about cilia assembly, little is understood about the mechanisms of their maintenance. Given that intraflagellar transport (IFT) is essential for cilium assembly, we investigated the role of one of its main players, IFT88, in ciliary maintenance. We show that DmIFT88, the Drosophila melanogaster orthologue of IFT88, continues to move along fully formed sensory cilia, and that its acute knockdown in the ciliated neurons of the adult affects sensory behaviour. We further identify DmGucy2d, the Drosophila guanylyl cyclase 2d, as a DmIFT88 cargo, whose loss also leads to defects in sensory behaviour maintenance. DmIFT88 binds to the intracellular part of DmGucy2d, a highly, evolutionarily conserved and mutated in several degenerative retina diseases, taking the cyclase into the cilia. Our results offer a novel mechanism for the maintenance of sensory cilia function and its potential role in human diseases.

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Faculty Opinions recommendation of Critical role of cyclophilin A and its prolyl-peptidyl isomerase activity in the structure and function of the hepatitis C virus replication complex.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.1162955.623591 ◽

2009 ◽

Author(s):

Teresa Compton

Keyword(s):

Hepatitis C Virus ◽

Hepatitis C ◽

Virus Replication ◽

Critical Role ◽

Cyclophilin A ◽

Structure And Function ◽

Replication Complex ◽

Isomerase Activity ◽

And Function

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MicroRNAs in Cardiac Autophagy: Small Molecules and Big Role

Cells ◽

10.3390/cells7080104 ◽

2018 ◽

Vol 7 (8) ◽

pp. 104 ◽

Cited By ~ 22

Author(s):

Teng Sun ◽

Meng-Yang Li ◽

Pei-Feng Li ◽

Ji-Min Cao

Keyword(s):

Cardiac Fibrosis ◽

Heart Diseases ◽

Critical Role ◽

Transcriptional Gene Silencing ◽

Close Link ◽

Post Transcriptional Gene Silencing ◽

Evolutionarily Conserved ◽

Cardiac Disorders ◽

Cellular Components

Autophagy, which is an evolutionarily conserved process according to the lysosomal degradation of cellular components, plays a critical role in maintaining cell homeostasis. Autophagy and mitochondria autophagy (mitophagy) contribute to the preservation of cardiac homeostasis in physiological settings. However, impaired or excessive autophagy is related to a variety of diseases. Recently, a close link between autophagy and cardiac disorders, including myocardial infarction, cardiac hypertrophy, cardiomyopathy, cardiac fibrosis, and heart failure, has been demonstrated. MicroRNAs (miRNAs) are a class of small non-coding RNAs with a length of approximately 21–22 nucleotides (nt), which are distributed widely in viruses, plants, protists, and animals. They function in mediating the post-transcriptional gene silencing. A growing number of studies have demonstrated that miRNAs regulate cardiac autophagy by suppressing the expression of autophagy-related genes in a targeted manner, which are involved in the pathogenesis of heart diseases. This review summarizes the role of microRNAs in cardiac autophagy and related cardiac disorders. Furthermore, we mainly focused on the autophagy regulation pathways, which consisted of miRNAs and their targeted genes.

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TRPV channel OCR-2 is distributed along C. elegans chemosensory cilia by diffusion in a local interplay with intraflagellar transport

10.1101/2020.11.19.390005 ◽

2020 ◽

Author(s):

Jaap van Krugten ◽

Noémie Danné ◽

Erwin J.G. Peterman

Keyword(s):

Single Molecule ◽

Transmembrane Proteins ◽

Intraflagellar Transport ◽

Single Molecule Tracking ◽

C Elegans ◽

Normal Diffusion ◽

Cellular Signal ◽

Underlying Mechanisms ◽

And Function

AbstractSensing and reacting to the environment is essential for survival and procreation of most organisms. Caenorhabditis elegans senses soluble chemicals with transmembrane proteins (TPs) in the cilia of its chemosensory neurons. Development, maintenance and function of these cilia relies on intraflagellar transport (IFT), in which motor proteins transport cargo, including sensory TPs, back and forth along the ciliary axoneme. Here we use live fluorescence imaging to show that IFT machinery and the sensory TP OCR-2 reversibly redistribute along the cilium after exposure to repellant chemicals. To elucidate the underlying mechanisms, we performed single-molecule tracking experiments and found that OCR-2 distribution depends on an intricate interplay between IFT-driven transport, normal diffusion and subdiffusion that depends on the specific location in the cilium. These insights in the role of IFT on the dynamics of cellular signal transduction contribute to a deeper understanding of the regulation of sensory TPs and chemosensing.

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A Review on Role of Macro and Micro Banking Environment on Non-Performing Assets Management

Behavioral Finance and Decision-Making Models - Advances in Finance, Accounting, and Economics ◽

10.4018/978-1-5225-7399-9.ch016 ◽

2019 ◽

pp. 281-294

Author(s):

Biswajit Prasad Chhatoi ◽

Sharada Prasad Sahoo

Keyword(s):

Critical Role ◽

Banking System ◽

Financial Assets ◽

Policy Changes ◽

Public And Private ◽

Private Banks ◽

Specific Factors ◽

And Function ◽

Asset Creation

In a self-resilient economy, banking system assumes importance in imparting momentum to economic growth and prosperity through mobilization of financial assets. Performance of banks, irrespective of their nature and function, is germane to their asset creation and maintenance capacity. In a neo-liberal regime, radical policy changes have crept into loan mechanism, thereby subjecting the banks to efficiently recover the loans, which is a vital asset for any banking firm. In this context, the authors through intensive review of literature identified micro and macro banking factors responsible for productive NPA management. The macro banking factors refer to the economic environment whereas the micro banking factors refer to the bank and branch-specific factors. The authors identified the critical role of organizational structure, involvement of employees, and organizational efficiency in driving prudent NPA management. The authors have found that the efficiency in managing NPAs differ in public and private banks, which is attributed to involvement of employees.

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Critical role of histone H3 lysine 27 demethylase Kdm6b in the homeostasis and function of medullary thymic epithelial cells

Cell Death and Differentiation ◽

10.1038/s41418-020-0546-8 ◽

2020 ◽

Vol 27 (10) ◽

pp. 2843-2855

Author(s):

Zhi Liu ◽

Haohao Zhang ◽

Yiming Hu ◽

Dandan Liu ◽

Lingling Li ◽

...

Keyword(s):

Epithelial Cells ◽

Critical Role ◽

Histone H3 ◽

Thymic Epithelial Cells ◽

Medullary Thymic Epithelial Cells ◽

And Function

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The role of the cerebellum in creativity and expert stone knapping

Adaptive Behavior ◽

10.1177/1059712320966462 ◽

2020 ◽

pp. 105971232096646

Author(s):

Frederick L Coolidge

Keyword(s):

Critical Role ◽

Brain Regions ◽

Stone Tool ◽

Fine Motor ◽

Engagement Theory ◽

Motor Movements ◽

And Function ◽

The Mind ◽

Stone Knapping

The purpose of this article is to review the evolution and function of the cerebellum, particularly in regard to its role in creativity and expert stone knapping. First, the article reviews the history of the cerebellum, its evolution and phylogenetics, and its concerted evolution with various brain regions. It also notes the critical role of the cerebellum and the cerebro-cerebellar network in its traditionally recognized control of gross and fine motor movements and in its exaptation for basic and higher level cognitive processes, particularly in regard to increasingly more sophisticated stone knapping. Also, reviewed are various theories, advanced over the past three decades, of how the cerebellum tweaks and refines thoughts, images, and ideas just as it refines and smooths motor movements. Baddeley’s working memory model is also prominently featured, as are the works of Ito, Vandervert, and others on the cerebellum’s role in novel problem-solving, insight, and creativity. Finally, this article reviews two “Cognitive Rubicons” in stone tool knapping, Theory of Mind and stone knapping, and Malafouris’ Material Engagement Theory. The article concludes with a novel hypothesis that the automaticity provided by the cerebellum derived from extensive practice in stone knapping may have freed Baddeley’s central executive from its attentional demands and allows the mind to “wander and wonder.”

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