scholarly journals Mitochondrial trafficking and anchoring in neurons: New insight and implications

2014 ◽  
Vol 204 (7) ◽  
pp. 1087-1098 ◽  
Author(s):  
Zu-Hang Sheng
Keyword(s):  
Energy Source ◽  
Recent Work ◽  
Neurological Disorders ◽  
Synaptic Function ◽  
Local Energy ◽  
Synaptic Physiology ◽  
Mitochondrial Motility ◽  
Mitochondrial Trafficking ◽  
And Function ◽  
Neuron Growth

Mitochondria are essential organelles for neuronal growth, survival, and function. Neurons use specialized mechanisms to drive mitochondria transport and to anchor them in axons and at synapses. Stationary mitochondria buffer intracellular Ca2+ and serve as a local energy source by supplying ATP. The balance between motile and stationary mitochondria responds quickly to changes in axonal and synaptic physiology. Defects in mitochondrial transport are implicated in the pathogenesis of several major neurological disorders. Recent work has provided new insight in the regulation of microtubule-based mitochondrial trafficking and anchoring, and on how mitochondrial motility influences neuron growth, synaptic function, and mitophagy.

scholarly journals Role of MicroRNA in Governing Synaptic Plasticity

2016 ◽  
Vol 2016 ◽  
pp. 1-13 ◽  
Author(s):  
Yuqin Ye ◽  
Hongyu Xu ◽  
Xinhong Su ◽  
Xiaosheng He
Keyword(s):  
Synaptic Plasticity ◽  
Neurological Disorders ◽  
Therapeutic Strategy ◽  
Target Gene ◽  
Synaptic Function ◽  
The Novel ◽  
Individual Mirnas ◽  
Underlying Mechanisms ◽  
And Function

Although synaptic plasticity in neural circuits is orchestrated by an ocean of genes, molecules, and proteins, the underlying mechanisms remain poorly understood. Recently, it is well acknowledged that miRNA exerts widespread regulation over the translation and degradation of target gene in nervous system. Increasing evidence suggests that quite a few specific miRNAs play important roles in various respects of synaptic plasticity including synaptogenesis, synaptic morphology alteration, and synaptic function modification. More importantly, the miRNA-mediated regulation of synaptic plasticity is not only responsible for synapse development and function but also involved in the pathophysiology of plasticity-related diseases. A review is made here on the function of miRNAs in governing synaptic plasticity, emphasizing the emerging regulatory role of individual miRNAs in synaptic morphological and functional plasticity, as well as their implications in neurological disorders. Understanding of the way in which miRNAs contribute to synaptic plasticity provides rational clues in establishing the novel therapeutic strategy for plasticity-related diseases.

scholarly journals The Role of Deubiquitinating Enzymes in Synaptic Function and Nervous System Diseases

2012 ◽  
Vol 2012 ◽  
pp. 1-13 ◽  
Author(s):  
Jennifer R. Kowalski ◽  
Peter Juo
Keyword(s):  
Neurological Disorders ◽  
Ubiquitin Ligases ◽  
Synaptic Function ◽  
Deubiquitinating Enzymes ◽  
Reversible Modification ◽  
And Function ◽  
Identification And Characterization ◽  
Free Ubiquitin

Posttranslational modification of proteins by ubiquitin has emerged as a critical regulator of synapse development and function. Ubiquitination is a reversible modification mediated by the concerted action of a large number of specific ubiquitin ligases and ubiquitin proteases, called deubiquitinating enzymes (DUBs). The balance of activity of these enzymes determines the localization, function, and stability of target proteins. While some DUBs counter the action of specific ubiquitin ligases by removing ubiquitin and editing ubiquitin chains, other DUBs function more generally to maintain the cellular pool of free ubiquitin monomers. The importance of DUB function at the synapse is underscored by the association of specific mutations in DUB genes with several neurological disorders. Over the last decade, although much research has led to the identification and characterization of many ubiquitin ligases at the synapse, our knowledge of the relevant DUBs that act at the synapse has lagged. This review is focused on highlighting our current understanding of DUBs that regulate synaptic function and the diseases that result from dysfunction of these DUBs.

First person – Fanny Jaudon and Martina Albini

2021 ◽  
Vol 134 (16) ◽  
Keyword(s):  
Neurotrophic Factor ◽  
Neurological Disorders ◽  
Molecular Mechanisms ◽  
Neurological Diseases ◽  
Early Career ◽  
First Person ◽  
Early Career Researchers ◽  
And Function ◽  
The University ◽  
Selection Of

ABSTRACT First Person is a series of interviews with the first authors of a selection of papers published in Journal of Cell Science, helping early-career researchers promote themselves alongside their papers. Fanny Jaudon and Martina Albini are co-first authors on ‘ A developmental stage- and Kidins220-dependent switch in astrocyte responsiveness to brain-derived neurotrophic factor’, published in JCS. Fanny is a postdoc at the University of Trieste in the lab of Lorenzo A. Cingolani at Center for Synaptic Neuroscience and Technology, Istituto Italiano di Tecnologia, Genova, Italy, investigating the molecular mechanisms controlling development and function of neuronal circuits and implementing genome-editing approaches for the treatment of neurological disorders. Martina is a PhD student at the Istituto Italiano di Tecnologia in the lab of Fabio Benfenati and Fabrizia Cesca investigating neurotrophin biology and its involvement in neurological diseases.

William Rutherford Sanders (1828–1881), anatomist, physician, linguist and museum conservator

2018 ◽  
Vol 28 (2) ◽  
pp. 120-123
Author(s):  
Dugald Gardner
Keyword(s):  
Neurological Disorders ◽  
Later Life ◽  
Structure And Function ◽  
Royal Infirmary ◽  
Abdominal Abscess ◽  
General Pathology ◽  
Consultant Physician ◽  
University Of Edinburgh ◽  
And Function ◽  
The University

William Rutherford Sanders spent a childhood and early student days divided between Edinburgh and Montpelier, France before graduating in Medicine in Edinburgh. An early interest in the spleen was encouraged by a two-year period in Europe where he became familiar with the work of Helmholtz, Bernard and Henle. Returning to Edinburgh, his growing experience led to the position of assistant in the Infirmary pathology department. He conducted classes in the University of Edinburgh and on behalf of the Royal Colleges became familiar with the museum of the Royal College of Surgeons where he was chosen as Conservator in 1853. Criticised by 20th century historians for concentrating on verbal teaching rather than on the conservation of the museum, Sanders became a consultant physician to the Royal Infirmary in 1861 and in 1869 Professor of General Pathology. Throughout these years, Sanders gave as much time as possible to the study of the structure and function of the spleen and to neurological disorders such as hemiplegia. His later life was interrupted by a series of illnesses commencing with an abdominal abscess. A prolonged convalescence allowed the resumption of work but deranged vision and hemiplegia preceded his death on 18 February 1881.

scholarly journals cAMP-stimulated phosphorylation of diaphanous 1 regulates protein stability and interaction with binding partners in adrenocortical cells

2013 ◽  
Vol 24 (6) ◽  
pp. 848-857 ◽  
Author(s):  
Donghui Li ◽  
Eric B. Dammer ◽  
Natasha C. Lucki ◽  
Marion B. Sewer
Keyword(s):  
Oxysterol Binding Protein ◽  
Mitochondrial Movement ◽  
Binding Partners ◽  
Extracellular Signal ◽  
Camp Signaling Pathway ◽  
Integral Role ◽  
Mitochondrial Trafficking ◽  
The Stability ◽  
And Function ◽  
Β Tubulin

Diaphanous homologue 1 (DIAPH1) is a Rho effector protein that coordinates cellular dynamics by regulating microfilament and microtubule function. We previously showed that DIAPH1 plays an integral role in regulating the production of cortisol by controlling the rate of mitochondrial movement, by which activation of the adrenocorticotropin (ACTH)/cAMP signaling pathway stimulates mitochondrial trafficking and promotes the interaction between RhoA and DIAPH1. In the present study we use mass spectrometry to identify DIAPH1 binding partners and find that DIAPH1 interacts with several proteins, including RhoA, dynamin-1, kinesin, β-tubulin, β-actin, oxysterol-binding protein (OSBP)–related protein 2 (ORP2), and ORP10. Moreover, DIAPH1 is phosphorylated in response to dibutyryl cAMP (Bt2cAMP) at Thr-759 via a pathway that requires extracellular signal-related kinase (ERK). Alanine substitution of Thr-759 renders DIAPH1 more stable and attenuates the interaction between DIAPH1 and kinesin, ORP2, and actin but has no effect on the ability of the protein to interact with RhoA or β-tubulin. Finally, overexpression of a DIAPH1 T759A mutant significantly decreases the rate of Bt2cAMP-stimulated mitochondrial movement. Taken together, our findings establish a key role for phosphorylation in regulating the stability and function of DIAPH1.

scholarly journals CSPα reduces aggregates and rescues striatal dopamine release in αsynuclein transgenic mice

2020 ◽  
Author(s):  
L Caló ◽  
E Hidari ◽  
M Wegrzynowicz ◽  
JW Dalley ◽  
BL Schneider ◽  
...  
Keyword(s):  
Dopamine Release ◽  
Early Stage ◽  
Synaptic Function ◽  
Snare Complex ◽  
Early Event ◽  
Vesicle Recycling ◽  
Cysteine String Protein ◽  
And Function

AbstractαSynuclein aggregation at the synapse is an early event in Parkinson’s disease and is associated with impaired striatal synaptic function and dopaminergic neuronal death. The cysteine string protein (CSPα) and αsynuclein have partially overlapping roles in maintaining synaptic function and mutations in each cause neurodegenerative diseases. CSPα is a member of the DNAJ/HSP40 family of co-chaperones and like αsynuclein, chaperones the SNARE complex assembly and neurotransmitter release. αSynuclein can rescue neurodegeneration in CSPαKO mice. However, whether αsynuclein aggregation alters CSPα expression and function is unknown. Here we show that αsynuclein aggregation at the synapse induces a decrease in synaptic CSPα and a reduction in the complexes that CSPα forms with HSC70 and STGa. We further show that viral delivery of CSPα rescues in vitro the impaired vesicle recycling in PC12 cells with αsynuclein aggregates and in vivo reduces synaptic αsynuclein aggregates restoring normal dopamine release in 1-120hαsyn mice. These novel findings reveal a mechanism by which αsynuclein aggregation alters CSPα at the synapse, and show that CSPα rescues αsynuclein aggregation-related phenotype in 1-120hαsyn mice similar to the effect of αsynuclein in CSPαKO mice. These results implicate CSPα as a potential therapeutic target for the treatment of early-stage PD.

scholarly journals Mitochondrial Fission Protein 1: Emerging Roles in Organellar Form and Function in Health and Disease

2021 ◽  
Vol 12 ◽  
Author(s):  
Ugochukwu Kelvin Ihenacho ◽  
Kelsey A. Meacham ◽  
Megan Cleland Harwig ◽  
Michael E. Widlansky ◽  
R. Blake Hill
Keyword(s):  
Human Health ◽  
Neurological Disorders ◽  
Mitochondrial Fission ◽  
Cell Types ◽  
Mitochondrial Division ◽  
Form And Function ◽  
Health And Disease ◽  
Genetic Deletion ◽  
And Function

Mitochondrial fission protein 1 (Fis1) was identified in yeast as being essential for mitochondrial division or fission and subsequently determined to mediate human mitochondrial and peroxisomal fission. Yet, its exact functions in humans, especially in regard to mitochondrial fission, remains an enigma as genetic deletion of Fis1 elongates mitochondria in some cell types, but not others. Fis1 has also been identified as an important component of apoptotic and mitophagic pathways suggesting the protein may have multiple, essential roles. This review presents current perspectives on the emerging functions of Fis1 and their implications in human health and diseases, with an emphasis on Fis1’s role in both endocrine and neurological disorders.

scholarly journals Regulation of mitochondria-dynactin interaction and mitochondrial retrograde transport in axons

eLife ◽  
2017 ◽  
Vol 6 ◽  
Author(s):  
Catherine M Drerup ◽  
Amy L Herbert ◽  
Kelly R Monk ◽  
Alex V Nechiporuk
Keyword(s):  
Neural Circuit ◽  
Genetic Interaction ◽  
Retrograde Transport ◽  
Genetic Screen ◽  
Binding Domain ◽  
Loss Of Function ◽  
Mitochondrial Transport ◽  
Interaction Studies ◽  
Mitochondrial Motility ◽  
And Function

Mitochondrial transport in axons is critical for neural circuit health and function. While several proteins have been found that modulate bidirectional mitochondrial motility, factors that regulate unidirectional mitochondrial transport have been harder to identify. In a genetic screen, we found a zebrafish strain in which mitochondria fail to attach to the dynein retrograde motor. This strain carries a loss-of-function mutation in actr10, a member of the dynein-associated complex dynactin. The abnormal axon morphology and mitochondrial retrograde transport defects observed in actr10 mutants are distinct from dynein and dynactin mutant axonal phenotypes. In addition, Actr10 lacking the dynactin binding domain maintains its ability to bind mitochondria, arguing for a role for Actr10 in dynactin-mitochondria interaction. Finally, genetic interaction studies implicated Drp1 as a partner in Actr10-dependent mitochondrial retrograde transport. Together, this work identifies Actr10 as a factor necessary for dynactin-mitochondria interaction, enhancing our understanding of how mitochondria properly localize in axons.

NDE1 and GSK3β Associate with TRAK1 and Regulate Axonal Mitochondrial Motility: Identification of Cyclic AMP as a Novel Modulator of Axonal Mitochondrial Trafficking

2016 ◽  
Vol 7 (5) ◽  
pp. 553-564 ◽  
Author(s):  
Fumiaki Ogawa ◽  
Laura C. Murphy ◽  
Elise L. V. Malavasi ◽  
Shane T. O’Sullivan ◽  
Helen S. Torrance ◽  
...  
Keyword(s):  
Cyclic Amp ◽  
Mitochondrial Motility ◽  
Mitochondrial Trafficking

scholarly journals Sleep-wake cycles drive daily dynamics of synaptic phosphorylation

Science ◽  
2019 ◽  
Vol 366 (6462) ◽  
pp. eaav3617 ◽  
Author(s):  
Franziska Brüning ◽  
Sara B. Noya ◽  
Tanja Bange ◽  
Stella Koutsouli ◽  
Jan D. Rudolph ◽  
...  
Keyword(s):  
Brain Function ◽  
Synaptic Function ◽  
Synaptic Activity ◽  
Regulation Of Transcription ◽  
Protein Abundance ◽  
Cellular Processes ◽  
Cytoskeleton Reorganization ◽  
And Function ◽  
Daily Changes ◽  
Rest Activity

The circadian clock drives daily changes of physiology, including sleep-wake cycles, through regulation of transcription, protein abundance, and function. Circadian phosphorylation controls cellular processes in peripheral organs, but little is known about its role in brain function and synaptic activity. We applied advanced quantitative phosphoproteomics to mouse forebrain synaptoneurosomes isolated across 24 hours, accurately quantifying almost 8000 phosphopeptides. Half of the synaptic phosphoproteins, including numerous kinases, had large-amplitude rhythms peaking at rest-activity and activity-rest transitions. Bioinformatic analyses revealed global temporal control of synaptic function through phosphorylation, including synaptic transmission, cytoskeleton reorganization, and excitatory/inhibitory balance. Sleep deprivation abolished 98% of all phosphorylation cycles in synaptoneurosomes, indicating that sleep-wake cycles rather than circadian signals are main drivers of synaptic phosphorylation, responding to both sleep and wake pressures.

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