scholarly journals Autoinhibition of kinesin-1 is essential to the dendrite-specific localization of Golgi outposts

2018 ◽  
Vol 217 (7) ◽  
pp. 2531-2547 ◽  
Author(s):  
Michael T. Kelliher ◽  
Yang Yue ◽  
Ashley Ng ◽  
Daichi Kamiyama ◽  
Bo Huang ◽  
...  
Keyword(s):  
Drosophila Melanogaster ◽  
Structure Function ◽  
Genetic Interaction ◽  
Function Analysis ◽  
Molecular Motor ◽  
Neuronal Polarity ◽  
Growth Defects ◽  
Specific Localization ◽  
Selective Localization

Neuronal polarity relies on the selective localization of cargo to axons or dendrites. The molecular motor kinesin-1 moves cargo into axons but is also active in dendrites. This raises the question of how kinesin-1 activity is regulated to maintain the compartment-specific localization of cargo. Our in vivo structure–function analysis of endogenous Drosophila melanogaster kinesin-1 reveals a novel role for autoinhibition in enabling the dendrite-specific localization of Golgi outposts. Mutations that disrupt kinesin-1 autoinhibition result in the axonal mislocalization of Golgi outposts. Autoinhibition also regulates kinesin-1 localization. Uninhibited kinesin-1 accumulates in axons and is depleted from dendrites, correlating with the change in outpost distribution and dendrite growth defects. Genetic interaction tests show that a balance of kinesin-1 inhibition and dynein activity is necessary to localize Golgi outposts to dendrites and keep them from entering axons. Our data indicate that kinesin-1 activity is precisely regulated by autoinhibition to achieve the selective localization of dendritic cargo.

scholarly journals Autoinhibition of kinesin-1 is essential to the dendrite-specific localization of Golgi outposts

2018 ◽  
Author(s):  
Michael T. Kelliher ◽  
Yang Yue ◽  
Ashley Ng ◽  
Daichi Kamiyama ◽  
Bo Huang ◽  
...  
Keyword(s):  
Structure Function ◽  
Molecular Motors ◽  
Genetic Interaction ◽  
Function Analysis ◽  
Molecular Motor ◽  
Neuronal Polarity ◽  
Growth Defects ◽  
Specific Localization ◽  
Selective Localization

AbstractNeuronal polarity relies on the selective localization of cargo to axons or dendrites. The molecular motor kinesin-1 moves cargo into axons but is also active in dendrites. This raises the question of how kinesin-1 activity is regulated to maintain the compartment-specific localization of cargo. Our in vivo structure-function analysis of endogenous Drosophila kinesin-1 reveals a novel role for autoinhibition in enabling the dendrite-specific localization of Golgi outposts. Mutations that disrupt kinesin-1 autoinhibition result in the axonal mislocalization of Golgi outposts. Autoinhibition also regulates kinesin-1 localization. Uninhibited kinesin-1 accumulates in axons and is depleted from dendrites, correlating with the change in outpost distribution and dendrite growth defects. Genetic interaction tests show that a balance of kinesin-1 inhibition and dynein activity is necessary to localize Golgi outposts to dendrites and keep them from entering axons. Our data indicate that kinesin-1 activity is precisely regulated by autoinhibition to achieve the selective localization of dendritic cargo.SummaryNeuronal polarity relies on the axon-or dendrite-specific localization of cargo by molecular motors such as kinesin-1. These studies show autoinhibition regulates both kinesin-1 activity and localization to keep dendritic cargo from entering axons.

scholarly journals Regulated nuclear import of the Drosophila rel protein dorsal: structure-function analysis.

1996 ◽  
Vol 16 (3) ◽  
pp. 1103-1114 ◽  
Author(s):  
S Govind ◽  
E Drier ◽  
L H Huang ◽  
R Steward
Keyword(s):  
Amino Acids ◽  
Structure Function ◽  
Nuclear Localization ◽  
Nuclear Import ◽  
Function Analysis ◽  
Drosophila Embryo ◽  
Nuclear Targeting ◽  
Homology Region ◽  
Early Drosophila Embryo

The formation of a gradient of nuclear Dorsal protein in the early Drosophila embryo is the last step in a maternally encoded dorsal-ventral signal transduction pathway. This gradient is formed in response to a ventral signal, which leads to the dissociation of cytoplasmic Dorsal from the I kappa B homolog Cactus. Free Dorsal is then targeted to the nucleus. Dorsal is a Rel-family transcription factor. Signal-dependent nuclear localization characterizes the regulation of Rel proteins. In order to identify regions of Dorsal that are essential for its homodimerization, nuclear targeting, and interaction with Cactus, we have performed an in vivo structure-function analysis. Our results show that all these functions are carried out by regions within the conserved Rel-homology region of Dorsal. The C-terminal divergent half of Dorsal is dispensable for its selective nuclear import. A basic stretch of 6 amino acids at the C terminus of the Rel-homology region is necessary for nuclear localization. This nuclear localization signal is not required for Cactus binding. Removal of the N-terminal 40 amino acids abolished the nuclear import of Dorsal, uncovering a potentially novel function for this highly conserved region.

scholarly journals Discrete Functions of TRAF1 and TRAF2 in Drosophila melanogaster Mediated by c-Jun N-Terminal Kinase and NF-κB-Dependent Signaling Pathways

2003 ◽  
Vol 23 (22) ◽  
pp. 7982-7991 ◽  
Author(s):  
Guang-Ho Cha ◽  
Kyoung Sang Cho ◽  
Jun Hee Lee ◽  
Myungjin Kim ◽  
Euysoo Kim ◽  
...  
Keyword(s):  
Drosophila Melanogaster ◽  
Signaling Pathways ◽  
Nuclear Translocation ◽  
Genetic Interaction ◽  
Ectopic Expression ◽  
Tumor Necrosis Factor Receptor ◽  
Null Mutant ◽  
Microbial Infection ◽  
Jnk Pathway

ABSTRACT Two Drosophila tumor necrosis factor receptor-associated factors (TRAF), DTRAF1 and DTRAF2, are proposed to have similar functions with their mammalian counterparts as a signal mediator of cell surface receptors. However, their in vivo functions and related signaling pathways are not fully understood yet. Here, we show that DTRAF1 is an in vivo regulator of c-Jun N-terminal kinase (JNK) pathway in Drosophila melanogaster. Ectopic expression of DTRAF1 in the developing eye induced apoptosis, thereby causing a rough-eye phenotype. Further genetic interaction analyses revealed that the apoptosis in the eye imaginal disc and the abnormal eye morphogenesis induced by DTRAF1 are dependent on JNK and its upstream kinases, Hep and DTAK1. In support of these results, DTRAF1-null mutant showed a remarkable reduction in JNK activity with an impaired development of imaginal discs and a defective formation of photosensory neuron arrays. In contrast, DTRAF2 was demonstrated as an upstream activator of nuclear factor-κB (NF-κB). Ectopic expression of DTRAF2 induced nuclear translocation of two Drosophila NF-κBs, DIF and Relish, consequently activating the transcription of the antimicrobial peptide genes diptericin, diptericin-like protein, and drosomycin. Consistently, the null mutant of DTRAF2 showed immune deficiencies in which NF-κB nuclear translocation and antimicrobial gene transcription against microbial infection were severely impaired. Collectively, our findings demonstrate that DTRAF1 and DTRAF2 play pivotal roles in Drosophila development and innate immunity by differentially regulating the JNK- and the NF-κB-dependent signaling pathway, respectively.

scholarly journals Structure/Function Analysis of the Vaccinia Virus F18 Phosphoprotein, an Abundant Core Component Required for Virion Maturation and Infectivity

2010 ◽  
Vol 84 (13) ◽  
pp. 6846-6860 ◽  
Author(s):  
Nadi T. Wickramasekera ◽  
Paula Traktman
Keyword(s):  
Amino Acids ◽  
Structure Function ◽  
Protein Interactions ◽  
Function Analysis ◽  
Aromatic Amino Acids ◽  
Protein Protein Interactions ◽  
Core Component ◽  
Virion Morphogenesis

ABSTRACT Poxvirus virions, whose outer membrane surrounds two lateral bodies and a core, contain at least 70 different proteins. The F18 phosphoprotein is one of the most abundant core components and is essential for the assembly of mature virions. We report here the results of a structure/function analysis in which the role of conserved cysteine residues, clusters of charged amino acids and clusters of hydrophobic/aromatic amino acids have been assessed. Taking advantage of a recombinant virus in which F18 expression is IPTG (isopropyl-β-d-thiogalactopyranoside) dependent, we developed a transient complementation assay to evaluate the ability of mutant alleles of F18 to support virion morphogenesis and/or to restore the production of infectious virus. We have also examined protein-protein interactions, comparing the ability of mutant and WT F18 proteins to interact with WT F18 and to interact with the viral A30 protein, another essential core component. We show that F18 associates with an A30-containing multiprotein complex in vivo in a manner that depends upon clusters of hydrophobic/aromatic residues in the N′ terminus of the F18 protein but that it is not required for the assembly of this complex. Finally, we confirmed that two PSSP motifs within F18 are the sites of phosphorylation by cellular proline-directed kinases in vitro and in vivo. Mutation of both of these phosphorylation sites has no apparent impact on virion morphogenesis but leads to the assembly of virions with significantly reduced infectivity.

In silico investigation of Methyl parathion and Diazinon with different Metabolic protein in Drosophila melanogaster

2021 ◽  
pp. 3794-3798
Author(s):  
Suman Sahoo ◽  
Md. Lutfur Rahman ◽  
Sagarika Mitra ◽  
Rajiniraja M.
Keyword(s):  
Drosophila Melanogaster ◽  
Protein Function ◽  
Methyl Parathion ◽  
Function Analysis ◽  
Glutathione S Transferase ◽  
Agriculture Industry ◽  
Bimolecular Interactions ◽  
Metabolic Protein ◽  
Chemical Pollutant

Chemical pollutant such as insecticide, pesticide and drugs are mainly used for agriculture, industry and economic development, which are well known for environment pollutant due to its toxicity and persistence in the nature. It can accumulate into the environment and continuously contaminate the food chain which causes threat to the health of consumer including human. Based on all these studies our investigation deals with the effects of two insecticides viz. methyl parathion and diazinon to non target organism like Drosophila melanogaster. In this study we have performed molecular modeling, docking and protein function analysis of different metabolic and physiological enzyme of Drosophila melanogaster such as acetylcholinesterase (AchE), Glutathione S-transferase D1(GST) and Protein kinase C (PKC) with these insecticides of six combinations (AchE + Diazinon, AchE + methyl parathion, GST+Diazinon, GST+Methyl parathion, PKC+Diazinon, PKC+Methyl parathion). Molecular docking results showing best binding affinity for GST+ Methyl parathion with binding energy of -4.79 kcal/mol. Overall, methyl parathion produces efficient binding toward all target protein when compare to diazinon. However, more detailed analysis need to be carried out to have an in-depth understanding of in vivo significance of these bimolecular interactions.

scholarly journals In vivo structure-function analysis of Drosophila HAIRLESS

1997 ◽  
Vol 67 (1) ◽  
pp. 97-106 ◽  
Author(s):  
Dieter Maier ◽  
Jörg Marquart ◽  
Annick Thompson-Fontaine ◽  
Irmtraud Beck ◽  
Elisa Wurmbach ◽  
...  
Keyword(s):  
Structure Function ◽  
Function Analysis

scholarly journals Structure-function analysis of the Drosophila melanogaster Caudal transcription factor provides insights into core promoter-preferential activation.

2015 ◽  
Vol 290 (34) ◽  
pp. 20747-20747 ◽  
Author(s):  
Hila Shir-Shapira ◽  
Julia Sharabany ◽  
Matan Filderman ◽  
Diana Ideses ◽  
Avital Ovadia-Shochat ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Drosophila Melanogaster ◽  
Structure Function ◽  
Function Analysis ◽  
Core Promoter ◽  
Preferential Activation

scholarly journals In vivo structure-function analysis of human Dicer reveals directional processing of precursor miRNAs

RNA ◽  
2012 ◽  
Vol 18 (6) ◽  
pp. 1116-1122 ◽  
Author(s):  
A. M. Gurtan ◽  
V. Lu ◽  
A. Bhutkar ◽  
P. A. Sharp
Keyword(s):  
Structure Function ◽  
Function Analysis ◽  
Precursor Mirnas

scholarly journals Structure-function analysis of β-arrestin Kurtz reveals a critical role of receptor interactions in downregulation of GPCR signaling in vivo

2019 ◽  
Vol 455 (2) ◽  
pp. 409-419 ◽  
Author(s):  
Fei Chai ◽  
Wenjian Xu ◽  
Timothy Musoke ◽  
George Tarabelsi ◽  
Steven Assaad ◽  
...  
Keyword(s):  
Structure Function ◽  
Function Analysis ◽  
Critical Role ◽  
Gpcr Signaling ◽  
Receptor Interactions
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