The Histone Demethylase KDM5 is Required for Synaptic Structure and Function at The  Drosophila Neuromuscular Junction

2020 ◽  
Author(s):  
Helen Belalcazar ◽  
Emily Hendricks ◽  
Sumaira Zamurrad ◽  
Faith Liebl ◽  
Julie Secombe
Keyword(s):  
Neuromuscular Junction ◽  
Structure And Function ◽  
Histone Demethylase ◽  
Synaptic Structure ◽  
And Function

scholarly journals The histone demethylase KDM5 is required for synaptic structure and function at the Drosophila neuromuscular junction

Cell Reports ◽  
2021 ◽  
Vol 34 (7) ◽  
pp. 108753 ◽  
Author(s):  
Helen M. Belalcazar ◽  
Emily L. Hendricks ◽  
Sumaira Zamurrad ◽  
Faith L.W. Liebl ◽  
Julie Secombe
Keyword(s):  
Neuromuscular Junction ◽  
Structure And Function ◽  
Histone Demethylase ◽  
Synaptic Structure ◽  
And Function

scholarly journals Glial Cells Maintain Synaptic Structure and Function and Promote Development of the Neuromuscular Junction In Vivo

Neuron ◽  
2003 ◽  
Vol 40 (3) ◽  
pp. 563-580 ◽  
Author(s):  
Linga V. Reddy ◽  
Samir Koirala ◽  
Yoshie Sugiura ◽  
Albert A. Herrera ◽  
Chien-Ping Ko
Keyword(s):  
Neuromuscular Junction ◽  
Glial Cells ◽  
Structure And Function ◽  
Synaptic Structure ◽  
And Function

scholarly journals The histone demethylase KDM5 is required for synaptic structure and function at the Drosophila neuromuscular junction

2020 ◽  
Author(s):  
Helen M. Belalcazar ◽  
Emily L. Hendricks ◽  
Sumaira Zamurrad ◽  
Faith L.W. Liebl ◽  
Julie Secombe
Keyword(s):  
Neuromuscular Junction ◽  
Histone Demethylase ◽  
Synaptic Function ◽  
Complex Nature ◽  
Synaptic Structure ◽  
Genes Encoding ◽  
Demethylase Activity ◽  
Larval Neuromuscular Junction ◽  
And Function ◽  
Structure And Activity

SummaryMutations in the genes encoding the KDM5 family of histone demethylases are observed in individuals with intellectual disability (ID). Despite clear evidence linking KDM5 function to neurodevelopmental pathways, how this family of proteins impacts transcriptional programs to mediate synaptic structure and activity remains unclear. Using the Drosophila larval neuromuscular junction (NMJ), we show that KDM5 is required for neuroanatomical development and synaptic function. The JmjC-domain encoded histone demethylase activity of KDM5, which is expected to be diminished by many ID-associated alleles and required for appropriate synaptic morphology and neurotransmission. The C5HC2 zinc finger of KDM5 is also involved, as an ID-associated mutation in this motif reduces NMJ bouton number but increases bouton size. KDM5 therefore uses demethylase-dependent and independent mechanisms to regulate NMJ structure and activity, highlighting the complex nature by which this chromatin modifier carries out its neuronal gene regulatory programs.

scholarly journals Regulation of synaptic structure and function by palmitoylated AMPA receptor binding protein

2010 ◽  
Vol 43 (4) ◽  
pp. 341-352 ◽  
Author(s):  
Charu Misra ◽  
Sophie Restituito ◽  
Jainne Ferreira ◽  
Gerald A. Rameau ◽  
Jie Fu ◽  
...  
Keyword(s):  
Ampa Receptor ◽  
Receptor Binding ◽  
Binding Protein ◽  
Structure And Function ◽  
Synaptic Structure ◽  
Ampa Receptor Binding Protein ◽  
And Function ◽  
Receptor Binding Protein

Consequences of Pharmacological BACE Inhibition on Synaptic Structure and Function

2018 ◽  
Vol 84 (7) ◽  
pp. 478-487 ◽  
Author(s):  
Kaichuan Zhu ◽  
Finn Peters ◽  
Severin Filser ◽  
Jochen Herms
Keyword(s):  
Structure And Function ◽  
Synaptic Structure ◽  
And Function

scholarly journals Effect of salbutamol on neuromuscular junction function and structure in a mouse model of DOK7 congenital myasthenia

2020 ◽  
Vol 29 (14) ◽  
pp. 2325-2336 ◽  
Author(s):  
Richard G Webster ◽  
An E Vanhaesebrouck ◽  
Susan E Maxwell ◽  
Judith A Cossins ◽  
Weiwei Liu ◽  
...  
Keyword(s):  
Weight Gain ◽  
Neuromuscular Junction ◽  
Mouse Model ◽  
Structural Integrity ◽  
Ex Vivo ◽  
Adrenergic Agonists ◽  
Mice Model ◽  
Synaptic Structure ◽  
Perinatal Lethality ◽  
And Function

Abstract Congenital myasthenic syndromes (CMS) are characterized by fatigable muscle weakness resulting from impaired neuromuscular transmission. β2-adrenergic agonists are an effective treatment for DOK7-CMS. DOK7 is a component within the AGRN-LRP4-MUSK-DOK7 signalling pathway that is key for the formation and maintenance of the synaptic structure of the neuromuscular junction (NMJ). The precise mechanism of action of β2-adrenergic agonists at the NMJ is not fully understood. In this study, we investigated whether β2-adrenergic agonists improve both neurotransmission and structural integrity of the NMJ in a mouse model of DOK7-CMS. Ex-vivo electrophysiological techniques and microscopy of the NMJ were used to study the effect of salbutamol, a β2-adrenergic agonist, on synaptic structure and function. DOK7-CMS model mice displayed a severe phenotype with reduced weight gain and perinatal lethality. Salbutamol treatment improved weight gain and survival in DOK7 myasthenic mice. Model animals had fewer active NMJs, detectable by endplate recordings, compared with age-matched wild-type littermates. Salbutamol treatment increased the number of detectable NMJs during endplate recording. Correspondingly, model mice had fewer acetylcholine receptor-stained NMJs detected by fluorescent labelling, but following salbutamol treatment an increased number were detectable. The data demonstrate that salbutamol can prolong survival and increase NMJ number in a severe model of DOK7-CMS.

Synaptopathy: dysfunction of synaptic function?

2010 ◽  
Vol 38 (2) ◽  
pp. 443-444 ◽  
Author(s):  
Nils Brose ◽  
Vincent O'Connor ◽  
Paul Skehel
Keyword(s):  
Animal Experimentation ◽  
Structure And Function ◽  
Synaptic Function ◽  
Cellular Systems ◽  
Brain Diseases ◽  
Psychiatric Disease ◽  
Synaptic Dysfunction ◽  
A Value ◽  
Synaptic Structure ◽  
And Function

Synaptopathy is an increasingly popular term used to define key features of neurodegenerative and psychiatric disease. It implies that disruptions in synaptic structure and function are potentially the major determinant of such brain diseases. The Synaptopathies: Dysfunction of Synaptic Function Biochemical Society Focused Meeting brought together several invited speakers, supplemented with short communications from young scientists, who addressed this possibility. The talks spanned the full gamut of approaches that brought molecular, cellular, systems and whole-animal experimentation together to address how fundamental synaptic biology was increasingly informing on dysfunction in disease. The disease and models thereof discussed included Alzheimer's disease, prions, Huntington's disease, Parkinson's disease, schizophrenia and autism. The audience were asked to reflect on whether synaptopathy, although attractive and conceptually useful, provided a significant explanation as the cause of these major diseases. The breadth of the meeting reinforced the complexity of these brain diseases, supported the significance of synaptic dysfunction in disease, but left open the issue as to whether the prime cause of these disorders could be resolved as simple synaptic dysfunction. Thus, despite revealing a value of synaptopathy, further investigation will be required to reveal its balance in the cause and effect in each of the major brain diseases.

Sign in / Sign up

Export Citation Format

Share Document