scholarly journals Excitation-contraction coupling and its relation to synaptic dysfunction in Drosophila

2020 ◽  
Author(s):  
Kiel G. Ormerod ◽  
Anthony E. Scibelli ◽  
J. Troy Littleton
Keyword(s):  
Muscle Performance ◽  
Synaptic Dysfunction ◽  
Muscle Contractility ◽  
Detailed Characterization ◽  
Synaptic Development ◽  
Excitation Contraction Coupling ◽  
Contraction Coupling ◽  
And Function ◽  
Identification And Characterization

AbstractThe Drosophila neuromuscular system is widely used to characterize synaptic development and function. However, little is known about how specific synaptic deficits alter neuromuscular transduction and muscle contractility that ultimately dictate behavioural output. Here we develop a system for detailed characterization of excitation-contraction coupling at Drosophila larval NMJs and demonstrate how specific synaptic and neuronal manipulations disrupt muscle contractility. Muscle contraction force increases with motoneuron stimulation frequency and duration, showing considerable plasticity between 5-40 Hz, while saturating above 50 Hz. Temperature is negatively correlated with muscle performance and enhanced at lower temperatures. A screen for modulators of muscle contractility led to the identification and characterization of the molecular and cellular pathway by which a specific FMRFa peptide, TPAEDFMRFa, increases muscle performance. These findings indicate Drosophila NMJs provide a robust system to relate synaptic dysfunction to alterations in excitation-contraction coupling.

scholarly journals Distinct Phosphoisoforms of the XenopusMcm4 Protein Regulate the Function of the Mcm Complex

2000 ◽  
Vol 20 (10) ◽  
pp. 3667-3676 ◽  
Author(s):  
Inna Pereverzeva ◽  
Elizabeth Whitmire ◽  
Bettina Khan ◽  
Martine Coué
Keyword(s):  
Cell Cycle ◽  
Cyclin B ◽  
Detailed Characterization ◽  
Cyclin Dependent Kinases ◽  
Origins Of Replication ◽  
Mcm Complex ◽  
Initiation Of Dna Replication ◽  
And Function ◽  
Mitotic Phosphorylation

ABSTRACT Initiation of DNA replication in eukaryotes requires the assembly of prereplication complexes (pre-Rcs) at the origins of replication. The assembly and function of the pre-Rcs appear to be controlled by phosphorylation events. In this study we report the detailed characterization of the cell cycle phosphorylation of one component of the Xenopus pre-Rcs, the Mcm protein complex. We show that individual Mcm subunits are differentially phosphorylated during the cell cycle. During mitosis, the Mcm4 subunit is hyperphosphorylated, while the other subunits are not actively phosphorylated. The mitotic phosphorylation of Mcm4 requires Cdc2-cyclin B and other unknown kinases. Following exit from mitosis, the Mcm4 subunit of the cytosolic interphase complex undergoes dephosphorylation, and the Mcm2, Mcm3, or Mcm6 subunits are then actively phosphorylated by kinase(s) other than cyclin-dependent kinases (Cdks) or Cdc7. The association of the Mcm complex with the pre-Rcs correlates with the formation of a transient interphase complex. This complex contains an intermediately phosphorylated Mcm4 subunit and is produced by partial dephosphorylation of the mitotic hyperphosphorylated Mcm4 protein. Complete dephosphorylation of the Mcm4 subunit inactivates the Mcm complex and prevents its binding to the chromatin. Once the Mcm complex is assembled on the chromatin the Mcm4 and the Mcm2 proteins are the only subunits phosphorylated during the activation of the pre-Rcs. These chromatin-associated phosphorylations require nuclear transport and are independent of Cdk2-cyclin E. These results suggest that the changes in Mcm4 phosphorylation regulate pre-Rc assembly and the function of the pre-Rcs on the chromatin.

scholarly journals Postgenomic Scan of Metallo-β-Lactamase Homologues in Rhizobacteria: Identification and Characterization of BJP-1, a Subclass B3 Ortholog from Bradyrhizobium japonicum

2006 ◽  
Vol 50 (6) ◽  
pp. 1973-1981 ◽  
Author(s):  
Magdalena Stoczko ◽  
Jean-Marie Frère ◽  
Gian Maria Rossolini ◽  
Jean-Denis Docquier
Keyword(s):  
Bradyrhizobium Japonicum ◽  
Catalytic Efficiency ◽  
Open Reading Frames ◽  
Human Pathogens ◽  
Microbial Genomes ◽  
E Coli ◽  
Genes Encoding ◽  
And Function ◽  
Identification And Characterization

ABSTRACT The diffusion of metallo-β-lactamases (MBLs) among clinically important human pathogens represents a therapeutic issue of increasing importance. However, the origin of these resistance determinants is largely unknown, although an important number of proteins belonging to the MBL superfamily have been identified in microbial genomes. In this work, we analyzed the distribution and function of genes encoding MBL-like proteins in the class Rhizobiales. Among 12 released complete genomes of members of the class Rhizobiales, a total of 57 open reading frames (ORFs) were found to have the MBL conserved motif and identity scores with MBLs ranging from 8 to 40%. On the basis of the best identity scores with known MBLs, four ORFs were cloned into Escherichia coli for heterologous expression. Among their products, one (blr6230) encoded by the Bradyrhizobium japonicum USDA110 genome, named BJP-1, hydrolyzed β-lactams when expressed in E. coli. BJP-1 enzyme is most closely related to the CAU-1 enzyme from Caulobacter vibrioides (40% amino acid sequence identity), a member of subclass B3 MBLs. A kinetic analysis revealed that BJP-1 efficiently hydrolyzed most β-lactam substrates, except aztreonam, ticarcillin, and temocillin, with the highest catalytic efficiency measured with meropenem. Compared to other MBLs, BJP-1 was less sensitive to inactivation by chelating agents.

SCO-ping Out the Mechanisms Underlying the Etiology of Hydrocephalus

Physiology ◽  
2009 ◽  
Vol 24 (2) ◽  
pp. 117-126 ◽  
Author(s):  
Michael S. Huh ◽  
Matthew A. M. Todd ◽  
David J. Picketts
Keyword(s):  
Disease Gene ◽  
Subcommissural Organ ◽  
Clinical Problem ◽  
Gene Identification ◽  
Transgenic Mouse Models ◽  
Heterogeneous Nature ◽  
And Function ◽  
Identification And Characterization ◽  
Common Clinical Problem

The heterogeneous nature of congenital hydrocephalus has hampered our understanding of the molecular basis of this common clinical problem. However, disease gene identification and characterization of multiple transgenic mouse models has highlighted the importance of the subcommissural organ (SCO) and the ventricular ependymal (vel) cells. Here, we review how altered development and function of the SCO and vel cells contributes to hydrocephalus.

scholarly journals hnRNP U protein is required for normal pre-mRNA splicing and postnatal heart development and function

2015 ◽  
Vol 112 (23) ◽  
pp. E3020-E3029 ◽  
Author(s):  
Junqiang Ye ◽  
Nadine Beetz ◽  
Sean O’Keeffe ◽  
Juan Carlos Tapia ◽  
Lindsey Macpherson ◽  
...  
Keyword(s):  
Alternative Splicing ◽  
Heart Development ◽  
Specific Protein ◽  
Protein Product ◽  
Conclusive Evidence ◽  
Mrna Splicing ◽  
Excitation Contraction Coupling ◽  
Contraction Coupling ◽  
Hnrnp U ◽  
And Function

We report that mice lacking the heterogeneous nuclear ribonucleoprotein U (hnRNP U) in the heart develop lethal dilated cardiomyopathy and display numerous defects in cardiac pre-mRNA splicing. Mutant hearts have disorganized cardiomyocytes, impaired contractility, and abnormal excitation–contraction coupling activities. RNA-seq analyses of Hnrnpu mutant hearts revealed extensive defects in alternative splicing of pre-mRNAs encoding proteins known to be critical for normal heart development and function, including Titin and calcium/calmodulin-dependent protein kinase II delta (Camk2d). Loss of hnRNP U expression in cardiomyocytes also leads to aberrant splicing of the pre-mRNA encoding the excitation–contraction coupling component Junctin. We found that the protein product of an alternatively spliced Junctin isoform is N-glycosylated at a specific asparagine site that is required for interactions with specific protein partners. Our findings provide conclusive evidence for the essential role of hnRNP U in heart development and function and in the regulation of alternative splicing.

scholarly journals Recent Advances in the Discovery and Function of Antimicrobial Molecules in Platelets

2021 ◽  
Vol 22 (19) ◽  
pp. 10230
Author(s):  
Alba S. Aquino-Domínguez ◽  
María de los A. Romero-Tlalolini ◽  
Honorio Torres-Aguilar ◽  
Sergio R. Aguilar-Ruiz
Keyword(s):  
Antimicrobial Properties ◽  
Human Platelets ◽  
Rabbit Serum ◽  
Functional Evaluation ◽  
Host Defense Peptides ◽  
Vascular Integrity ◽  
Activated Platelets ◽  
And Function ◽  
Identification And Characterization

The conventional function described for platelets is maintaining vascular integrity. Nevertheless, increasing evidence reveals that platelets can additionally play a crucial role in responding against microorganisms. Activated platelets release molecules with antimicrobial activity. This ability was first demonstrated in rabbit serum after coagulation and later in rabbit platelets stimulated with thrombin. Currently, multiple discoveries have allowed the identification and characterization of PMPs (platelet microbicidal proteins) and opened the way to identify kinocidins and CHDPs (cationic host defense peptides) in human platelets. These molecules are endowed with microbicidal activity through different mechanisms that broaden the platelet participation in normal and pathologic conditions. Therefore, this review aims to integrate the currently described platelet molecules with antimicrobial properties by summarizing the pathways towards their identification, characterization, and functional evaluation that have promoted new avenues for studying platelets based on kinocidins and CHDPs secretion.

Characterization of cardiomyocyte excitation–contraction coupling in the FVB/N-C57BL/6 intercrossed “Chocolate” brown mice

Life Sciences ◽  
2006 ◽  
Vol 80 (3) ◽  
pp. 187-192 ◽  
Author(s):  
Qun Li ◽  
Cindy X. Fang ◽  
Jennifer M. Nunn ◽  
Jesse Zhang ◽  
Karissa H. LaCour ◽  
...  
Keyword(s):  
Excitation Contraction Coupling ◽  
Contraction Coupling

scholarly journals Lineage Contribution of PDGFRα-Expressing Cells in the Developing Mouse Eye

2021 ◽  
Vol 2021 ◽  
pp. 1-10
Author(s):  
Deyi Zhuo ◽  
Yumei Diao ◽  
Xiaoqi Li ◽  
Yifei Huang ◽  
Liqiang Wang
Keyword(s):  
Stromal Cells ◽  
Eye Development ◽  
Early Embryogenesis ◽  
Detailed Characterization ◽  
Ocular Development ◽  
Fiber Cells ◽  
Retinal Astrocytes ◽  
Reporter Mice ◽  
And Function

PDGFRα signaling is critically important in ocular development. Previous data on PDGFRα lacks an expression map with high spatial and temporal resolution and lineage information. In this study, we aim to present a detailed PDGFRα expression and lineage map from early embryogenesis to adulthood. PDGFRα-CreER; mT/mG reporter mice were analyzed. mEGFP-positive cells contributed to multiple ocular lineages in a spatiotemporally regulated manner. A dynamic PDGFRα expression was identified in corneal stromal cells, lens epithelial cells, lens fiber cells, and retinal astrocytes during the entire period of eye development, while PDGFRα expression in retinal astrocytes from E17.5 onwards and in Müller glial cells was identified within two weeks after birth. By revealing detailed characterization of gene expression and function, we present a comprehensive map of PDGFRα-expressing cells in the eye for a better understanding of PDGFRα signaling’s role during eye development.

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