Synaptopathy: dysfunction of synaptic function?

2010 ◽  
Vol 38 (2) ◽  
pp. 443-444 ◽  
Author(s):  
Nils Brose ◽  
Vincent O'Connor ◽  
Paul Skehel

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.

2004 ◽  
Vol 18 (2) ◽  
pp. 167-183 ◽  
Author(s):  
Jianhua Zhang ◽  
Amy Moseley ◽  
Anil G. Jegga ◽  
Ashima Gupta ◽  
David P. Witte ◽  
...  

To understand the commitment of the genome to nervous system differentiation and function, we sought to compare nervous system gene expression to that of a wide variety of other tissues by gene expression database construction and mining. Gene expression profiles of 10 different adult nervous tissues were compared with that of 72 other tissues. Using ANOVA, we identified 1,361 genes whose expression was higher in the nervous system than other organs and, separately, 600 genes whose expression was at least threefold higher in one or more regions of the nervous system compared with their median expression across all organs. Of the 600 genes, 381 overlapped with the 1,361-gene list. Limited in situ gene expression analysis confirmed that identified genes did represent nervous system-enriched gene expression, and we therefore sought to evaluate the validity and significance of these top-ranked nervous system genes using known gene literature and gene ontology categorization criteria. Diverse functional categories were present in the 381 genes, including genes involved in intracellular signaling, cytoskeleton structure and function, enzymes, RNA metabolism and transcription, membrane proteins, as well as cell differentiation, death, proliferation, and division. We searched existing public sites and identified 110 known genes related to mental retardation, neurological disease, and neurodegeneration. Twenty-one of the 381 genes were within the 110-gene list, compared with a random expectation of 5. This suggests that the 381 genes provide a candidate set for further analyses in neurological and psychiatric disease studies and that as a field, we are as yet, far from a large-scale understanding of the genes that are critical for nervous system structure and function. Together, our data indicate the power of profiling an individual biologic system in a multisystem context to gain insight into the genomic basis of its structure and function.


2021 ◽  
Vol 134 (16) ◽  
Author(s):  
Robert Mahen

ABSTRACT To gain a holistic understanding of cellular function, we must understand not just the role of individual organelles, but also how multiple macromolecular assemblies function collectively. Centrioles produce fundamental cellular processes through their ability to organise cytoskeletal fibres. In addition to nucleating microtubules, centrioles form lesser-known polymers, termed rootlets. Rootlets were identified over a 100 years ago and have been documented morphologically since by electron microscopy in different eukaryotic organisms. Rootlet-knockout animals have been created in various systems, providing insight into their physiological functions. However, the precise structure and function of rootlets is still enigmatic. Here, I consider common themes of rootlet function and assembly across diverse cellular systems. I suggest that the capability of rootlets to form physical links from centrioles to other cellular structures is a general principle unifying their functions in diverse cells and serves as an example of how cellular function arises from collective organellar activity.


2010 ◽  
Vol 43 (4) ◽  
pp. 341-352 ◽  
Author(s):  
Charu Misra ◽  
Sophie Restituito ◽  
Jainne Ferreira ◽  
Gerald A. Rameau ◽  
Jie Fu ◽  
...  

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

eLife ◽  
2018 ◽  
Vol 7 ◽  
Author(s):  
Guanglin Xing ◽  
Moyi Li ◽  
Yichen Sun ◽  
Menglong Rui ◽  
Yan Zhuang ◽  
...  

Neuroligins are postsynaptic adhesion molecules that are essential for postsynaptic specialization and synaptic function. But the underlying molecular mechanisms of neuroligin functions remain unclear. We found that Drosophila Neuroligin 1 (DNlg1) regulates synaptic structure and function through WAVE regulatory complex (WRC)-mediated postsynaptic actin reorganization. The disruption of DNlg1, DNlg2, or their presynaptic partner neurexin (DNrx) led to a dramatic decrease in the amount of F-actin. Further study showed that DNlg1, but not DNlg2 or DNlg3, directly interacts with the WRC via its C-terminal interacting receptor sequence. That interaction is required to recruit WRC to the postsynaptic membrane to promote F-actin assembly. Furthermore, the interaction between DNlg1 and the WRC is essential for DNlg1 to rescue the morphological and electrophysiological defects in dnlg1 mutants. Our results reveal a novel mechanism by which the DNrx-DNlg1 trans-synaptic interaction coordinates structural and functional properties at the neuromuscular junction.


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