scholarly journals Drosophila Short stop as a paradigm for the role and regulation of spectraplakins

2017 ◽  
Author(s):  
Andre Voelzmann ◽  
Yu-Ting Liew ◽  
Yue Qu ◽  
Ines Hahn ◽  
Cristina Melero ◽  
...  
Keyword(s):  
Genetic Model ◽  
Current Knowledge ◽  
Fruit Fly ◽  
Model Organisms ◽  
Functional Domains ◽  
Cellular Functions ◽  
Comprehensive Overview ◽  
Characteristic Functional ◽  
Intracellular Organelles ◽  
Linker Molecules

AbstractSpectraplakins are evolutionarily well conserved cytoskeletal linker molecules that are true members of three protein families: plakins, spectrins and Gas2-like proteins. Spectraplakin genes encode at least 7 characteristic functional domains which are combined in a modular fashion into multiple isoforms, and which are responsible for an enormous breadth of cellular functions. These functions are related to the regulation of actin, microtubules, intermediate filaments, intracellular organelles, cell adhesions and signalling processes during the development and maintenance of a wide variety of tissues. To gain a deeper understanding of this enormous functional diversity, invertebrate genetic model organisms, such as the fruit fly Drosophila, can be used to develop concepts and mechanistic paradigms that can inform the investigation in higher animals or humans. Here we provide a comprehensive overview of our current knowledge of the Drosophila spectraplakin Short stop (Shot). We describe its functional domains and isoforms and compare them with those of the mammalian spectraplakins dystonin and MACF1. We then summarise its roles during the development and maintenance of the nervous system, epithelia, oocytes and muscles, taking care to compare and contrast mechanistic insights across these functions in the fly, but especially also with related functions of dystonin and MACF1 in mostly mammalian contexts. We hope that this review will improve the wider appreciation of how work on Drosophila Shot can be used as an efficient strategy to promote the fundamental concepts and mechanisms that underpin spectraplakin functions, with important implications for biomedical research into human disease.

Containment strategies for synthetic gene drive organisms and impacts on gene flow.

2021 ◽  
pp. 137-152
Author(s):  
Lei Pei ◽  
Markus Schmidt
Keyword(s):  
Gene Flow ◽  
Fungal Infections ◽  
Basic Research ◽  
Fruit Fly ◽  
Mitigation Strategies ◽  
Synthetic Gene ◽  
Model Organisms ◽  
Gene Drive ◽  
Comprehensive Overview ◽  
Gene Drives

Abstract Gene drives, particularly synthetic gene drives, may help to address some important challenges, by efficiently altering specific sections of DNA in entire populations of wild organisms. Here we review the current development of the synthetic gene drives, especially those RNA-guided synthetic gene drives based on the CRISPR nuclease Cas. Particular focuses are on their possible applications in agriculture (e.g. disease resistance, weed control management), ecosystem conservation (e.g. evasion species control), health (e.g. to combat insect-borne and fungal infections), and for basic research in model organisms (e.g. Saccharomyces, fruit fly, and zebra fish). The physical, chemical, biological, and ecological containment strategies that might help to confine these gene drive-modified organisms are then explored. The gene flow issues, those from gene drive-derived organisms to the environment, are discussed, while possible mitigation strategies for gene drive research are explored. Last but not least, the regulatory context and opinions from key stakeholders (regulators, scientists, and concerned organizations) are reviewed, aiming to provide a more comprehensive overview of the field.

scholarly journals In control of biology: of mice, men and Foxes

2006 ◽  
Vol 397 (2) ◽  
pp. 233-246 ◽  
Author(s):  
Patrick J. E. C. Wijchers ◽  
J. Peter H. Burbach ◽  
Marten P. Smidt
Keyword(s):  
Transcription Factors ◽  
Current Knowledge ◽  
Treatment Strategies ◽  
Model Organisms ◽  
Functional Protein ◽  
Comprehensive Overview ◽  
Developmental Defects ◽  
Forkhead Transcription Factors ◽  
Human Pathology ◽  
Forkhead Gene

Forkhead proteins comprise a highly conserved family of transcription factors, named after the original forkhead gene in Drosophila. To date, over 100 forkhead genes have been identified in a large variety of species, all sharing the evolutionary conserved ‘forkhead’ DNA-binding domain, and the cloning and characterization of forkhead genes have continued in recent years. Forkhead transcription factors regulate the expression of countless genes downstream of important signalling pathways in most, if not all, tissues and cell types. Recent work has provided novel insights into the mechanisms that contribute to their functional diversity, including functional protein domains and interactions of forkheads with other transcription factors. Studies using loss- and gain-of-function models have elucidated the role of forkhead factors in developmental biology and cellular functions such as metabolism, cell division and cell survival. The importance of forkhead transcription factors is underlined by the developmental defects observed in mutant model organisms, and multiple human disorders and cancers which can be attributed to mutations within members of the forkhead gene family. This review provides a comprehensive overview of current knowledge on forkhead transcription factors, from structural organization and regulatory mechanisms to cellular and developmental functions in mice and humans. Finally, we will discuss how novel insights gained from involvement of ‘Foxes’ in the mechanisms underlying human pathology may create new opportunities for treatment strategies.

scholarly journals Rest Is Required to Learn an Appetitively-Reinforced Operant Task in Drosophila

2021 ◽  
Vol 15 ◽  
Author(s):  
Timothy D. Wiggin ◽  
Yungyi Hsiao ◽  
Jeffrey B. Liu ◽  
Robert Huber ◽  
Leslie C. Griffith
Keyword(s):  
Operant Conditioning ◽  
Molecular Mechanisms ◽  
Genetic Model ◽  
Model Organism ◽  
Fruit Fly ◽  
Model Organisms ◽  
Valuable Insight ◽  
Reward Contingency ◽  
Neural Basis ◽  
Operant Task

Maladaptive operant conditioning contributes to development of neuropsychiatric disorders. Candidate genes have been identified that contribute to this maladaptive plasticity, but the neural basis of operant conditioning in genetic model organisms remains poorly understood. The fruit fly Drosophila melanogaster is a versatile genetic model organism that readily forms operant associations with punishment stimuli. However, operant conditioning with a food reward has not been demonstrated in flies, limiting the types of neural circuits that can be studied. Here we present the first sucrose-reinforced operant conditioning paradigm for flies. In the paradigm, flies walk along a Y-shaped track with reward locations at the terminus of each hallway. When flies turn in the reinforced direction at the center of the track, they receive a sucrose reward at the end of the hallway. Only flies that rest early in training learn the reward contingency normally. Flies rewarded independently of their behavior do not form a learned association but have the same amount of rest as trained flies, showing that rest is not driven by learning. Optogenetically-induced sleep does not promote learning, indicating that sleep itself is not sufficient for learning the operant task. We validated the sensitivity of this assay to detect the effect of genetic manipulations by testing the classic learning mutant dunce. Dunce flies are learning-impaired in the Y-Track task, indicating a likely role for cAMP in the operant coincidence detector. This novel training paradigm will provide valuable insight into the molecular mechanisms of disease and the link between sleep and learning.

scholarly journals Molecular Biology of Escherichia coli Shiga Toxins’ Effects on Mammalian Cells

Toxins ◽  
2020 ◽  
Vol 12 (5) ◽  
pp. 345 ◽  
Author(s):  
Christian Menge
Keyword(s):  
Escherichia Coli ◽  
Mammalian Cells ◽  
Time Course ◽  
Current Knowledge ◽  
Enterohemorrhagic Escherichia Coli ◽  
Mammalian Host ◽  
Target Cells ◽  
Cellular Functions ◽  
Comprehensive Overview ◽  
Shiga Toxins

Shiga toxins (Stxs), syn. Vero(cyto)toxins, are potent bacterial exotoxins and the principal virulence factor of enterohemorrhagic Escherichia coli (EHEC), a subset of Shiga toxin-producing E. coli (STEC). EHEC strains, e.g., strains of serovars O157:H7 and O104:H4, may cause individual cases as well as large outbreaks of life-threatening diseases in humans. Stxs primarily exert a ribotoxic activity in the eukaryotic target cells of the mammalian host resulting in rapid protein synthesis inhibition and cell death. Damage of endothelial cells in the kidneys and the central nervous system by Stxs is central in the pathogenesis of hemolytic uremic syndrome (HUS) in humans and edema disease in pigs. Probably even more important, the toxins also are capable of modulating a plethora of essential cellular functions, which eventually disturb intercellular communication. The review aims at providing a comprehensive overview of the current knowledge of the time course and the consecutive steps of Stx/cell interactions at the molecular level. Intervention measures deduced from an in-depth understanding of this molecular interplay may foster our basic understanding of cellular biology and microbial pathogenesis and pave the way to the creation of host-directed active compounds to mitigate the pathological conditions of STEC infections in the mammalian body.

scholarly journals Rest is Required to Learn an Appetitively-Reinforced Operant Task in Drosophila

2020 ◽  
Author(s):  
Timothy D. Wiggin ◽  
Yung-Yi Hsiao ◽  
Jeffrey B. Liu ◽  
Robert Huber ◽  
Leslie C. Griffith
Keyword(s):  
Drosophila Melanogaster ◽  
Operant Conditioning ◽  
Food Reward ◽  
Molecular Mechanisms ◽  
Genetic Model ◽  
Fruit Fly ◽  
Model Organisms ◽  
Neural Basis ◽  
Operant Task ◽  
Insight Into

ABSTRACTMaladaptive operant conditioning contributes to development of neuropsychiatric disorders. Candidate genes have been identified that contribute to this maladaptive plasticity, but the neural basis of operant conditioning in genetic model organisms remains poorly understood. The fruit fly Drosophila melanogaster is a versatile genetic model organism that readily forms operant associations with punishment stimuli. However, operant conditioning with a food reward has not been demonstrated in flies, limiting the types of neural circuits that can be studied. Here we present the first sucrose-reinforced operant conditioning paradigm for flies. Flies of both sexes walk along a Y-shaped track with reward locations at the terminus of each hallway. When flies turn in the reinforced direction at the center of the track, sucrose is presented at the end of the hallway. Only flies that rest during training show evidence of learning the reward contingency. Flies rewarded independently of their behavior do not form a learned association but have the same amount of rest as trained flies, showing that rest is not driven by learning. Optogenetically-induced rest does not promote learning, indicating that rest is not sufficient for learning the operant task. We validated the sensitivity of this assay to detect the effect of genetic manipulations by testing the classic learning mutant dunce. Dunce flies are learning impaired in the Y-Track task, indicating a likely role for cAMP in the operant coincidence detector. This novel training paradigm will provide valuable insight into the molecular mechanisms of disease and the link between sleep and learning.SIGNIFICANCE STATEMENTOperant conditioning and mental health are deeply intertwined: maladaptive conditioning contributes to many pathologies, while therapeutic operant conditioning is a frequently used tool in talk therapy. Unlike drug interventions which target molecules or mechanisms, it is not known how operant conditioning changes the brain to promote wellness or distress. To gain mechanistic insight into how this form of learning works, we developed a novel operant training task for the fruit fly Drosophila melanogaster. We made three key discoveries. First, flies are able to learn an operant task to find food reward. Second, rest during training is necessary for learning. Third, the dunce gene is necessary for both classical and operant conditioning in flies, indicating that they may share molecular mechanisms.

scholarly journals Autophagy inDrosophila: From Historical Studies to Current Knowledge

2014 ◽  
Vol 2014 ◽  
pp. 1-24 ◽  
Author(s):  
Nitha C. Mulakkal ◽  
Peter Nagy ◽  
Szabolcs Takats ◽  
Radu Tusco ◽  
Gábor Juhász ◽  
...  
Keyword(s):  
Current Knowledge ◽  
Fruit Fly ◽  
Degradation Process ◽  
Research Field ◽  
Model Organisms ◽  
Great Promise ◽  
Functional Studies ◽  
Atg Genes ◽  
The 1960S ◽  
New Research

The discovery of evolutionarily conserved Atg genes required for autophagy in yeast truly revolutionized this research field and made it possible to carry out functional studies on model organisms. Insects includingDrosophilaare classical and still popular models to study autophagy, starting from the 1960s. This review aims to summarize past achievements and our current knowledge about the role and regulation of autophagy inDrosophila, with an outlook to yeast and mammals. The basic mechanisms of autophagy in fruit fly cells appear to be quite similar to other eukaryotes, and the role that this lysosomal self-degradation process plays inDrosophilamodels of various diseases already made it possible to recognize certain aspects of human pathologies. Future studies in this complete animal hold great promise for the better understanding of such processes and may also help finding new research avenues for the treatment of disorders with misregulated autophagy.

scholarly journals Emerging Insights into the Metabolic Alterations in Aging Using Metabolomics

Metabolites ◽  
2019 ◽  
Vol 9 (12) ◽  
pp. 301 ◽  
Author(s):  
Sarika Srivastava
Keyword(s):  
Biomarker Discovery ◽  
Environmental Changes ◽  
Current Knowledge ◽  
Cellular Tissue ◽  
Model Organisms ◽  
Biological Mechanisms ◽  
Comprehensive Overview ◽  
Biomarkers Of Aging ◽  
Complex Biological Process ◽  
Novel Biomarkers

Metabolomics is the latest ‘omics’ technology and systems biology science that allows for comprehensive profiling of small-molecule metabolites in biological systems at a specific time and condition. Metabolites are cellular intermediate products of metabolic reactions, which reflect the ultimate response to genomic, transcriptomic, proteomic, or environmental changes in a biological system. Aging is a complex biological process that is characterized by a gradual and progressive decline in molecular, cellular, tissue, organ, and organismal functions, and it is influenced by a combination of genetic, environmental, diet, and lifestyle factors. The precise biological mechanisms of aging remain unknown. Metabolomics has emerged as a powerful tool to characterize the organism phenotypes, identify altered metabolites, pathways, novel biomarkers in aging and disease, and offers wide clinical applications. Here, I will provide a comprehensive overview of our current knowledge on metabolomics led studies in aging with particular emphasis on studies leading to biomarker discovery. Based on the data obtained from model organisms and humans, it is evident that metabolites associated with amino acids, lipids, carbohydrate, and redox metabolism may serve as biomarkers of aging and/or longevity. Current challenges and key questions that should be addressed in the future to advance our understanding of the biological mechanisms of aging are discussed.

The glycomes of Caenorhabditis elegans and other model organisms

2002 ◽  
Vol 69 ◽  
pp. 117-134 ◽  
Author(s):  
Stuart M. Haslam ◽  
David Gems ◽  
Howard R. Morris ◽  
Anne Dell
Keyword(s):  
Caenorhabditis Elegans ◽  
Current Knowledge ◽  
Structural Data ◽  
Model Organisms ◽  
Entire Genome ◽  
C Elegans ◽  
The Face ◽  
Area Of Concern ◽  
Nematode Worm

There is no doubt that the immense amount of information that is being generated by the initial sequencing and secondary interrogation of various genomes will change the face of glycobiological research. However, a major area of concern is that detailed structural knowledge of the ultimate products of genes that are identified as being involved in glycoconjugate biosynthesis is still limited. This is illustrated clearly by the nematode worm Caenorhabditis elegans, which was the first multicellular organism to have its entire genome sequenced. To date, only limited structural data on the glycosylated molecules of this organism have been reported. Our laboratory is addressing this problem by performing detailed MS structural characterization of the N-linked glycans of C. elegans; high-mannose structures dominate, with only minor amounts of complex-type structures. Novel, highly fucosylated truncated structures are also present which are difucosylated on the proximal N-acetylglucosamine of the chitobiose core as well as containing unusual Fucα1–2Gal1–2Man as peripheral structures. The implications of these results in terms of the identification of ligands for genomically predicted lectins and potential glycosyltransferases are discussed in this chapter. Current knowledge on the glycomes of other model organisms such as Dictyostelium discoideum, Saccharomyces cerevisiae and Drosophila melanogaster is also discussed briefly.

scholarly journals Bone morphogenetic proteins, breast cancer, and bone metastases: striking the right balance

2017 ◽  
Vol 24 (10) ◽  
pp. R349-R366 ◽  
Author(s):  
Catherine Zabkiewicz ◽  
Jeyna Resaul ◽  
Rachel Hargest ◽  
Wen Guo Jiang ◽  
Lin Ye
Keyword(s):  
Breast Cancer ◽  
Cancer Progression ◽  
Bone Morphogenetic Proteins ◽  
Therapeutic Potential ◽  
Current Knowledge ◽  
Breast Tumour ◽  
Cellular Functions ◽  
Foetal Development ◽  
Key Factor ◽  
The Right

Bone morphogenetic proteins (BMPs) belong to the TGF-β super family, and are essential for the regulation of foetal development, tissue differentiation and homeostasis and a multitude of cellular functions. Naturally, this has led to the exploration of aberrance in this highly regulated system as a key factor in tumourigenesis. Originally identified for their role in osteogenesis and bone turnover, attention has been turned to the potential role of BMPs in tumour metastases to, and progression within, the bone niche. This is particularly pertinent to breast cancer, which commonly metastasises to bone, and in which studies have revealed aberrations of both BMP expression and signalling, which correlate clinically with breast cancer progression. Ultimately a BMP profile could provide new prognostic disease markers. As the evidence suggests a role for BMPs in regulating breast tumour cellular function, in particular interactions with tumour stroma and the bone metastatic microenvironment, there may be novel therapeutic potential in targeting BMP signalling in breast cancer. This review provides an update on the current knowledge of BMP abnormalities and their implication in the development and progression of breast cancer, particularly in the disease-specific bone metastasis.

Neuroligin-2 as a central organizer of inhibitory synapses in health and disease

2020 ◽  
Vol 13 (663) ◽  
pp. eabd8379
Author(s):  
Heba Ali ◽  
Lena Marth ◽  
Dilja Krueger-Burg
Keyword(s):  
Synaptic Transmission ◽  
Synapse Formation ◽  
Current Knowledge ◽  
Protein Complexes ◽  
Inhibitory Synapses ◽  
Molecular Architecture ◽  
Cellular Functions ◽  
Altered Expression ◽  
Health And Disease ◽  
Flow Of Information

Postsynaptic organizational protein complexes play central roles both in orchestrating synapse formation and in defining the functional properties of synaptic transmission that together shape the flow of information through neuronal networks. A key component of these organizational protein complexes is the family of synaptic adhesion proteins called neuroligins. Neuroligins form transsynaptic bridges with presynaptic neurexins to regulate various aspects of excitatory and inhibitory synaptic transmission. Neuroligin-2 (NLGN2) is the only member that acts exclusively at GABAergic inhibitory synapses. Altered expression and mutations in NLGN2 and several of its interacting partners are linked to cognitive and psychiatric disorders, including schizophrenia, autism, and anxiety. Research on NLGN2 has fundamentally shaped our understanding of the molecular architecture of inhibitory synapses. Here, we discuss the current knowledge on the molecular and cellular functions of mammalian NLGN2 and its role in the neuronal circuitry that regulates behavior in rodents and humans.

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