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

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.

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

2006 ◽  
Vol 17 (11) ◽  
pp. 4801-4811 ◽  
Author(s):  
Evgeni Efimenko ◽  
Oliver E. Blacque ◽  
Guangshuo Ou ◽  
Courtney J. Haycraft ◽  
Bradley K. Yoder ◽  
...  
Keyword(s):  
Caenorhabditis Elegans ◽  
Aspartic Acid ◽  
Critical Role ◽  
Intraflagellar Transport ◽  
Bardet Biedl Syndrome ◽  
Evolutionarily Conserved ◽  
Sensory Cilia ◽  
Mutant Phenotypes ◽  
And Function

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.

scholarly journals Drosophila SLC22 Orthologs Related to OATs, OCTs, and OCTNs Regulate Development and Responsiveness to Oxidative Stress

2020 ◽  
Vol 21 (6) ◽  
pp. 2002 ◽  
Author(s):  
Darcy C. Engelhart ◽  
Priti Azad ◽  
Suwayda Ali ◽  
Jeffry C. Granados ◽  
Gabriel G. Haddad ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Drosophila Melanogaster ◽  
Organic Molecules ◽  
Fruit Fly ◽  
Evolutionary Analysis ◽  
Oxygen Species ◽  
Small Organic Molecules ◽  
Evolutionarily Conserved

The SLC22 family of transporters is widely expressed, evolutionarily conserved, and plays a major role in regulating homeostasis by transporting small organic molecules such as metabolites, signaling molecules, and antioxidants. Analysis of transporters in fruit flies provides a simple yet orthologous platform to study the endogenous function of drug transporters in vivo. Evolutionary analysis of Drosophila melanogaster putative SLC22 orthologs reveals that, while many of the 25 SLC22 fruit fly orthologs do not fall within previously established SLC22 subclades, at least four members appear orthologous to mammalian SLC22 members (SLC22A16:CG6356, SLC22A15:CG7458, CG7442 and SLC22A18:CG3168). We functionally evaluated the role of SLC22 transporters in Drosophila melanogaster by knocking down 14 of these genes. Three putative SLC22 ortholog knockdowns—CG3168, CG6356, and CG7442/SLC22A—did not undergo eclosion and were lethal at the pupa stage, indicating the developmental importance of these genes. Additionally, knocking down four SLC22 members increased resistance to oxidative stress via paraquat testing (CG4630: p < 0.05, CG6006: p < 0.05, CG6126: p < 0.01 and CG16727: p < 0.05). Consistent with recent evidence that SLC22 is central to a Remote Sensing and Signaling Network (RSSN) involved in signaling and metabolism, these phenotypes support a key role for SLC22 in handling reactive oxygen species.

Late-Onset Folie Simultanée in a Pair of Monozygotic Twins

1986 ◽  
Vol 148 (4) ◽  
pp. 463-465 ◽  
Author(s):  
Kenneth S. Kendler ◽  
Gillian Robinson ◽  
Mary McGuire ◽  
Mary P. Spellman
Keyword(s):  
Case Report ◽  
Psychiatric Illness ◽  
Potential Role ◽  
Late Onset ◽  
Monozygotic Twins

A case-report is presented of folie simultanée in a pair of female monozygotic twins with onset at the remarkable age of 81. The twins demonstrated no evidence of dementia or other psychopathology apart from delusions. Folie simultanée in monozygotic twins provides a model example of the potential role of genotype-environment correlation in the etiology of psychiatric illness.

scholarly journals Functional modulation of IFT kinesins extends the sensory repertoire of ciliated neurons in Caenorhabditis elegans

2006 ◽  
Vol 172 (5) ◽  
pp. 663-669 ◽  
Author(s):  
James E. Evans ◽  
Joshua J. Snow ◽  
Amy L. Gunnarson ◽  
Guangshuo Ou ◽  
Henning Stahlberg ◽  
...  
Keyword(s):  
Caenorhabditis Elegans ◽  
Intraflagellar Transport ◽  
Full Length ◽  
Sensory Stimuli ◽  
Sensory Cilia ◽  
Section Electron ◽  
Functional Modulation ◽  
Serial Section Electron Microscopy ◽  
Section Electron Microscopy ◽  
Ciliated Neurons

The diversity of sensory cilia on Caenorhabditis elegans neurons allows the animal to detect a variety of sensory stimuli. Sensory cilia are assembled by intraflagellar transport (IFT) kinesins, which transport ciliary precursors, bound to IFT particles, along the ciliary axoneme for incorporation into ciliary structures. Using fluorescence microscopy of living animals and serial section electron microscopy of high pressure–frozen, freeze-substituted IFT motor mutants, we found that two IFT kinesins, homodimeric OSM-3 kinesin and heterotrimeric kinesin II, function in a partially redundant manner to build full-length amphid channel cilia but are completely redundant for building full-length amphid wing (AWC) cilia. This difference reflects cilia-specific differences in OSM-3 activity, which serves to extend distal singlets in channel cilia but not in AWC cilia, which lack such singlets. Moreover, AWC-specific chemotaxis assays reveal novel sensory functions for kinesin II in these wing cilia. We propose that kinesin II is a “canonical” IFT motor, whereas OSM-3 is an “accessory” IFT motor, and that subtle changes in the deployment or actions of these IFT kinesins can contribute to differences in cilia morphology, cilia function, and sensory perception.

scholarly journals Pattern separation and tuning shift in human sensory cortex underlie fear memory

2021 ◽  
Author(s):  
Yuqi You ◽  
Lucas R. Novak ◽  
Kevin Clancy ◽  
Wen Li
Keyword(s):  
Late Onset ◽  
Piriform Cortex ◽  
Fear Memory ◽  
Pattern Separation ◽  
Sensory Cortex ◽  
Evolutionarily Conserved ◽  
Sensory Encoding ◽  
Underlying Mechanisms ◽  
Cortical System

ABSTRACTAnimal research has recognized the role of the sensory cortex in fear memory and two key underlying mechanisms—pattern separation and tuning shift. We interrogated these mechanisms in the human sensory cortex in an olfactory differential conditioning study with a delayed (9-day) retention test. Combining affective appraisal and olfactory psychophysics with functional magnetic resonance imaging (fMRI) multivoxel pattern analysis and voxel-based tuning analysis over a linear odor-morphing continuum, we confirmed affective and perceptual learning and memory and demonstrated associative plasticity in the human olfactory (piriform) cortex. Specifically, the piriform cortex exhibited immediate and lasting enhancement in pattern separation (between the conditioned stimuli/CS and neighboring non-CS) and late-onset yet lasting tuning shift towards the CS, especially in anxious individuals. These findings highlight an evolutionarily conserved sensory cortical system of fear memory, which can underpin sensory encoding of fear/threat and confer a sensory mechanism to the neuropathophysiology of anxiety.

Potential role of CC chemokine receptor 6 in prediction of late-onset cytomegalovirus infection following solid organ transplant

2015 ◽  
Vol 29 (6) ◽  
pp. 492-498 ◽  
Author(s):  
Jose F. Camargo ◽  
Mariangela R. Resende ◽  
Ricardo Zamel ◽  
William Klement ◽  
Alyajahan Bhimji ◽  
...  
Keyword(s):  
Chemokine Receptor ◽  
Cytomegalovirus Infection ◽  
Potential Role ◽  
Late Onset ◽  
Organ Transplant ◽  
Solid Organ Transplant ◽  
Solid Organ ◽  
Cc Chemokine ◽  
Cc Chemokine Receptor 6

scholarly journals The GATOR1 Complex Regulates Metabolic Homeostasis and the Response to Nutrient Stress in Drosophila melanogaster

2016 ◽  
Vol 6 (12) ◽  
pp. 3859-3867 ◽  
Author(s):  
Youheng Wei ◽  
Brad Reveal ◽  
Weili Cai ◽  
Mary A Lilly
Keyword(s):  
Drosophila Melanogaster ◽  
Amino Acid ◽  
Fat Body ◽  
Critical Role ◽  
Nutrient Stress ◽  
Animal Physiology ◽  
Evolutionarily Conserved ◽  
A Cell ◽  
Baseline Levels

Abstract TORC1 regulates metabolism and growth in response to a large array of upstream inputs. The evolutionarily conserved trimeric GATOR1 complex inhibits TORC1 activity in response to amino acid limitation. In humans, the GATOR1 complex has been implicated in a wide array of pathologies including cancer and hereditary forms of epilepsy. However, the precise role of GATOR1 in animal physiology remains largely undefined. Here, we characterize null mutants of the GATOR1 components nprl2, nprl3, and iml1 in Drosophila melanogaster. We demonstrate that all three mutants have inappropriately high baseline levels of TORC1 activity and decreased adult viability. Consistent with increased TORC1 activity, GATOR1 mutants exhibit a cell autonomous increase in cell growth. Notably, escaper nprl2 and nprl3 mutant adults have a profound locomotion defect. In line with a nonautonomous role in the regulation of systemic metabolism, expressing the Nprl3 protein in the fat body, a nutrient storage organ, and hemocytes but not muscles and neurons rescues the motility of nprl3 mutants. Finally, we show that nprl2 and nprl3 mutants fail to activate autophagy in response to amino acid limitation and are extremely sensitive to both amino acid and complete starvation. Thus, in Drosophila, in addition to maintaining baseline levels of TORC1 activity, the GATOR1 complex has retained a critical role in the response to nutrient stress. In summary, the TORC1 inhibitor GATOR1 contributes to multiple aspects of the development and physiology of Drosophila.

scholarly journals Mycobiome in the Gut: A Multiperspective Review

2020 ◽  
Vol 2020 ◽  
pp. 1-16 ◽  
Author(s):  
Voon Kin Chin ◽  
Voon Chen Yong ◽  
Pei Pei Chong ◽  
Syafinaz Amin Nordin ◽  
Rusliza Basir ◽  
...  
Keyword(s):  
Potential Role ◽  
Good Health ◽  
Research Area ◽  
Human Diseases ◽  
Fungal Metabolites ◽  
Multiple Perspectives ◽  
Human Gut ◽  
Sequencing Technologies ◽  
Actual Mechanism

Human gut is home to a diverse and complex microbial ecosystem encompassing bacteria, viruses, parasites, fungi, and other microorganisms that have an undisputable role in maintaining good health for the host. Studies on the interplay between microbiota in the gut and various human diseases remain the key focus among many researchers. Nevertheless, advances in sequencing technologies and computational biology have helped us to identify a diversity of fungal community that reside in the gut known as the mycobiome. Although studies on gut mycobiome are still in its infancy, numerous sources have reported its potential role in host homeostasis and disease development. Nonetheless, the actual mechanism of its involvement remains largely unknown and underexplored. Thus, in this review, we attempt to discuss the recent advances in gut mycobiome research from multiple perspectives. This includes understanding the composition of fungal communities in the gut and the involvement of gut mycobiome in host immunity and gut-brain axis. Further, we also discuss on multibiome interactions in the gut with emphasis on fungi-bacteria interaction and the influence of diet in shaping gut mycobiome composition. This review also highlights the relation between fungal metabolites and gut mycobiota in human homeostasis and the role of gut mycobiome in various human diseases. This multiperspective review on gut mycobiome could perhaps shed new light for future studies in the mycobiome research area.

scholarly journals hrT is required for cardiovascular development in zebrafish

Development ◽  
2002 ◽  
Vol 129 (21) ◽  
pp. 5093-5101 ◽  
Author(s):  
Daniel P. Szeto ◽  
Kevin J. P. Griffin ◽  
David Kimelman
Keyword(s):  
Late Onset ◽  
Cardiovascular Development ◽  
Lateral Plate ◽  
T Box ◽  
Vascular Morphogenesis ◽  
Developing Heart ◽  
Evolutionarily Conserved ◽  
Heart Formation ◽  
Cardiovascular Cells

The recently identified zebrafish T-box gene hrT is expressed in the developing heart and in the endothelial cells forming the dorsal aorta. Orthologs of hrT are expressed in cardiovascular cells fromDrosophila to mouse, suggesting that the function of hrT is evolutionarily conserved. The role of hrT in cardiovascular development, however, has not thus far been determined in any animal model. Using morpholino antisense oligonucleotides, we show that zebrafish embryos lacking hrT function have dysmorphic hearts and an absence of blood circulation. Although the early events in heart formation were normal inhrT morphant embryos, subsequently the hearts failed to undergo looping, and late onset defects in chamber morphology and gene expression were observed. In particular, we found that the loss of hrT function led to a dramatic upregulation of tbx5, a gene required for normal heart morphogenesis. Conversely, we show that overexpression of hrT causes a significant downregulation of tbx5, indicating that one key role ofhrT is to regulate the levels of tbx5. Secondly, we found that HrT is required to inhibit the expression of the blood lineage markersgata1 and gata2 in the most posterior lateral plate mesoderm. Finally, we show that HrT is required for vasculogenesis in the trunk, leading to similar vascular defects to those observed in midline mutants such as floating head. hrT expression in the vascular progenitors depends upon midline mesoderm, indicating that this expression is one important component of the response to a midline-derived signal during vascular morphogenesis.

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