Biochemical and structural mechanisms of regulation of Arf GTPases by endocytic GEFs (LB259)

Small guanosine triphosphatases (GTPases) of the Rab and Arf families are key regulators of vesicle formation and membrane trafficking. Membrane transport plays an important role in the central nervous system. In this regard, neurons require a constant flow of membranes for the correct distribution of receptors, for the precise composition of proteins and organelles in dendrites and axons, for the continuous exocytosis/endocytosis of synaptic vesicles and for the elimination of dysfunctional proteins. Thus, it is not surprising that Rab and Arf GTPases have been associated with neurodegenerative diseases such as Alzheimer’s and Parkinson’s. Both pathologies share characteristics such as the presence of protein aggregates and/or the fragmentation of the Golgi apparatus, hallmarks that have been related to both Rab and Arf GTPases functions. Despite their relationship with neurodegenerative disorders, very few studies have focused on the role of these GTPases in the pathogenesis of neurodegeneration. In this review, we summarize their importance in the onset and progression of Alzheimer’s and Parkinson’s diseases, as well as their emergence as potential therapeutical targets for neurodegeneration.

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Built to Last: Functional and Structural Mechanisms in the Moth Olfactory Network Mitigate Effects of Neural Injury

Brain Sciences ◽

10.3390/brainsci11040462 ◽

2021 ◽

Vol 11 (4) ◽

pp. 462

Author(s):

Charles B. Delahunt ◽

Pedro D. Maia ◽

J. Nathan Kutz

Keyword(s):

Brain Injuries ◽

Hebbian Learning ◽

Neuronal Damage ◽

Neural Systems ◽

Network Motifs ◽

Neural Firing ◽

Neural Injury ◽

Axonal Pathology ◽

Structural Mechanisms ◽

Axonal Swellings

Most organisms suffer neuronal damage throughout their lives, which can impair performance of core behaviors. Their neural circuits need to maintain function despite injury, which in particular requires preserving key system outputs. In this work, we explore whether and how certain structural and functional neuronal network motifs act as injury mitigation mechanisms. Specifically, we examine how (i) Hebbian learning, (ii) high levels of noise, and (iii) parallel inhibitory and excitatory connections contribute to the robustness of the olfactory system in the Manduca sexta moth. We simulate injuries on a detailed computational model of the moth olfactory network calibrated to data. The injuries are modeled on focal axonal swellings, a ubiquitous form of axonal pathology observed in traumatic brain injuries and other brain disorders. Axonal swellings effectively compromise spike train propagation along the axon, reducing the effective neural firing rate delivered to downstream neurons. All three of the network motifs examined significantly mitigate the effects of injury on readout neurons, either by reducing injury’s impact on readout neuron responses or by restoring these responses to pre-injury levels. These motifs may thus be partially explained by their value as adaptive mechanisms to minimize the functional effects of neural injury. More generally, robustness to injury is a vital design principle to consider when analyzing neural systems.

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Increased expression of ARF GTPases in prostate cancer tissue

SpringerPlus ◽

10.1186/s40064-015-1136-y ◽

2015 ◽

Vol 4 (1) ◽

Cited By ~ 11

Author(s):

Claire Morgan ◽

Paul D Lewis ◽

Lynda Hopkins ◽

Stephanie Burnell ◽

Howard Kynaston ◽

...

Keyword(s):

Prostate Cancer ◽

Cancer Tissue ◽

Prostate Cancer Tissue ◽

Arf Gtpases

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Structural Mechanisms of Gating in Ionotropic Glutamate Receptors

Biochemistry ◽

10.1021/acs.biochem.7b00891 ◽

2017 ◽

Vol 57 (3) ◽

pp. 267-276 ◽

Cited By ~ 36

Author(s):

Edward C. Twomey ◽

Alexander I. Sobolevsky

Keyword(s):

Glutamate Receptors ◽

Ionotropic Glutamate Receptors ◽

Structural Mechanisms

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Structural mechanisms of plastic deformation of amorphous alloys containing crystalline nanoparticles

Bulletin of the Russian Academy of Sciences Physics ◽

10.3103/s1062873807120106 ◽

2007 ◽

Vol 71 (12) ◽

pp. 1702-1707 ◽

Cited By ~ 5

Author(s):

A. M. Glezer ◽

S. E. Manaenkov ◽

I. E. Permyakova

Keyword(s):

Plastic Deformation ◽

Amorphous Alloys ◽

Structural Mechanisms ◽

Mechanisms Of Plastic Deformation

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Comparative analysis of plant isochorismate synthases reveals structural mechanisms underlying their distinct biochemical properties

Bioscience Reports ◽

10.1042/bsr20171457 ◽

2018 ◽

Vol 38 (2) ◽

Cited By ~ 8

Author(s):

Shohei Yokoo ◽

Seiya Inoue ◽

Nana Suzuki ◽

Naho Amakawa ◽

Hidenori Matsui ◽

...

Keyword(s):

Biochemical Properties ◽

Stress Conditions ◽

The Other ◽

Protein Accumulation ◽

Transcriptional Level ◽

Multiple Sequence ◽

Primary And Secondary Metabolites ◽

Transit Peptides ◽

Alignment Analysis ◽

Structural Mechanisms

Isochorismate synthase (ICS) converts chorismate into isochorismate, a precursor of primary and secondary metabolites including salicylic acid (SA). SA plays important roles in responses to stress conditions in plants. Many studies have suggested that the function of plant ICSs is regulated at the transcriptional level. In Arabidopsis thaliana, the expression of AtICS1 is induced by stress conditions in parallel with SA synthesis, and AtICS1 is required for SA synthesis. In contrast, the expression of NtICS is not induced when SA synthesis is activated in tobacco, and it is unlikely to be involved in SA synthesis. Studies on the biochemical properties of plant ICSs are limited, compared with those on transcriptional regulation. We analyzed the biochemical properties of four plant ICSs: AtICS1, NtICS, NbICS from Nicotiana benthamiana, and OsICS from rice. Multiple sequence alignment analysis revealed that their primary structures were well conserved, and predicted key residues for ICS activity were almost completely conserved. However, AtICS1 showed much higher activity than the other ICSs when expressed in Escherichia coli and N. benthamiana leaves. Moreover, the levels of AtICS1 protein expression in N. benthamiana leaves were higher than the other ICSs. Construction and analysis of chimeras between AtICS1 and OsICS revealed that the putative chloroplast transit peptides (TPs) significantly affected the levels of protein accumulation in N. benthamiana leaves. Chimeric and point-mutation analyses revealed that Thr531, Ser537, and Ile550 of AtICS1 are essential for its high activity. These distinct biochemical properties of plant ICSs may suggest different roles in their respective plant species.

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