scholarly journals Neuronal post-developmentally acting SAX-7S/L1CAM can function as cleaved fragments to maintain neuronal architecture in C. elegans

2021 ◽  
Author(s):  
V.E. Desse ◽  
C.R. Blanchette ◽  
P. Perrat ◽  
C.Y. Bénard

ABSTRACTWhereas remarkable advances have uncovered mechanisms that drive nervous system assembly, the processes responsible for the lifelong maintenance of nervous system architecture remain poorly understood. Subsequent to its establishment during embryogenesis, neuronal architecture is maintained throughout life in the face of the animal’s growth, maturation processes, the addition of new neurons, body movements, and aging. The C. elegans protein SAX-7, homologous to the vertebrate L1 protein family, is required for maintaining the organization of neuronal ganglia and fascicles after their successful initial embryonic development. To dissect the function of sax-7 in neuronal maintenance, we generated a null allele and sax-7S-isoform-specific alleles. We find that the null sax-7(qv30) is, in some contexts, more severe than previously described mutant alleles, and that the loss of sax-7S largely phenocopies the null, consistent with sax-7S being the key isoform in neuronal maintenance. Using a sfGFP::SAX-7S knock-in, we observe sax-7S to be predominantly expressed across the nervous system, from embryogenesis to adulthood. Yet, its role in maintaining neuronal organization is ensured by post-developmentally acting SAX-7S, as larval transgenic sax-7S(+) expression alone is sufficient to profoundly rescue the null mutants’ neuronal maintenance defects. Moreover, the majority of the protein SAX-7 appears to be cleaved, and we show that these cleaved SAX-7S fragments together, not individually, can fully support neuronal maintenance. These findings contribute to our understanding of the role of the conserved protein SAX-7/L1CAM in long-term neuronal maintenance, and may help decipher processes that go awry in some neurodegenerative conditions.

Genetics ◽  
2021 ◽  
Author(s):  
Virginie E Desse ◽  
Cassandra R Blanchette ◽  
Malika Nadour ◽  
Paola Perrat ◽  
Lise Rivollet ◽  
...  

Abstract Whereas remarkable advances have uncovered mechanisms that drive nervous system assembly, the processes responsible for the lifelong maintenance of nervous system architecture remain poorly understood. Subsequent to its establishment during embryogenesis, neuronal architecture is maintained throughout life in the face of the animal’s growth, maturation processes, the addition of new neurons, body movements, and aging. The C. elegans protein SAX-7, homologous to the vertebrate L1 protein family of neural adhesion molecules, is required for maintaining the organization of neuronal ganglia and fascicles after their successful initial embryonic development. To dissect the function of sax-7 in neuronal maintenance, we generated a null allele and sax-7S-isoform-specific alleles. We find that the null sax-7(qv30) is, in some contexts, more severe than previously described mutant alleles, and that the loss of sax-7S largely phenocopies the null, consistent with sax-7S being the key isoform in neuronal maintenance. Using a sfGFP::SAX-7S knock-in, we observe sax-7S to be predominantly expressed across the nervous system, from embryogenesis to adulthood. Yet, its role in maintaining neuronal organization is ensured by post-developmentally acting SAX-7S, as larval transgenic sax-7S(+) expression alone is sufficient to profoundly rescue the null mutants' neuronal maintenance defects. Moreover, the majority of the protein SAX-7 appears to be cleaved, and we show that these cleaved SAX-7S fragments together, not individually, can fully support neuronal maintenance. These findings contribute to our understanding of the role of the conserved protein SAX-7/L1CAM in long-term neuronal maintenance, and may help decipher processes that go awry in some neurodegenerative conditions.


1995 ◽  
Vol 73 (9-10) ◽  
pp. 575-592 ◽  
Author(s):  
Harish C. Pant ◽  
Veeranna

Neurofilament proteins (NFPs) are highly phosphorylated molecules in the axonal compartment of the adult nervous system. The phosphorylation of NFP is considered an important determinant of filament caliber, plasticity, and stability. This process reflects the function of NFs during the lifetime of a neuron from differentiation in the embryo through long-term activity in the adult until aging and environmental insult leads to pathology and ultimately death. NF function is modulated by phosphorylation–dephosphorylation in each of these diverse neuronal states. In this review, we have summarized some of these properties of NFP in adult nervous tissue, mostly from work in our own laboratory. Identification of sites phosphorylated in vivo in high molecular weight NFP (NF-H) and properties of NF-associated and neural-specific kinases phosphorylating specific sites in NFP are described. A model to explain the role of NF phosphorylation in determining filament caliber, plasticity, and stability is proposed.Key words: neurofilament proteins, phosphorylation, kinases, phosphatases, regulators, inhibitors, multimesic complex, domains.


1993 ◽  
Vol 6 (4) ◽  
pp. 181-185 ◽  
Author(s):  
W. D. Cutlip II ◽  
M. R. Leary

Although a common and occasionally troubling reaction, social blushing has received little systematic attention from either medical or behavioral researchers. This article reviews what is known of the physiological and psychological processes that mediate social blushing, and speculates regarding the role of central mechanisms in the phenomenon. Blushing is characterized by the unusual combination of cutaneous vasodilatation of the face, neck, and ears, accompanied by activation of the sympathetic nervous system. Psychologically, blushing appears to occur when people receive undesired social attention from others and may be analogous to the appeasement displays observed in non-human primates. Although poorly understood, the central mechanisms that mediate blushing obviously involve both involuntary autonomic effector systems and higher areas that involve self-reflective thought. Questions for future research are suggested.


Author(s):  
Alasdair Roberts

This chapter assesses the role of planning in the design of governance strategies. Enthusiasm for large-scale planning—also known as overall, comprehensive, long-term, economic, or social planning—boomed and collapsed in twentieth century. At the start of that century, progressive reformers seized on planning as the remedy for the United States' social and economic woes. By the end of the twentieth century, enthusiasm for large-scale planning had collapsed. Plans could be made, but they were unlikely to be obeyed, and even if they were obeyed, they were unlikely to work as predicted. The chapter then explains that leaders should make plans while being realistic about the limits of planning. It is necessary to exercise foresight, set priorities, and design policies that seem likely to accomplish those priorities. Simply by doing this, leaders encourage coordination among individuals and businesses, through conversation about goals and tactics. Neither is imperfect knowledge a total barrier to planning. There is no “law” of unintended consequences: it is not inevitable that government actions will produce entirely unexpected results. The more appropriate stance is modesty about what is known and what can be achieved. Plans that launch big schemes on brittle assumptions are more likely to fail. Plans that proceed more tentatively, that allow room for testing, learning, and adjustment, are less likely to collapse in the face of unexpected results.


2019 ◽  
Vol 7 (2) ◽  
pp. 8 ◽  
Author(s):  
DiLoreto ◽  
Chute ◽  
Bryce ◽  
Srinivasan

The complete structure and connectivity of the Caenorhabditis elegans nervous system (“mind of a worm”) was first published in 1986, representing a critical milestone in the field of connectomics. The reconstruction of the nervous system (connectome) at the level of synapses provided a unique perspective of understanding how behavior can be coded within the nervous system. The following decades have seen the development of technologies that help understand how neural activity patterns are connected to behavior and modulated by sensory input. Investigations on the developmental origins of the connectome highlight the importance of role of neuronal cell lineages in the final connectivity matrix of the nervous system. Computational modeling of neuronal dynamics not only helps reconstruct the biophysical properties of individual neurons but also allows for subsequent reconstruction of whole-organism neuronal network models. Hence, combining experimental datasets with theoretical modeling of neurons generates a better understanding of organismal behavior. This review discusses some recent technological advances used to analyze and perturb whole-organism neuronal function along with developments in computational modeling, which allows for interrogation of both local and global neural circuits, leading to different behaviors. Combining these approaches will shed light into how neural networks process sensory information to generate the appropriate behavioral output, providing a complete understanding of the worm nervous system.


2000 ◽  
Vol 11 (10) ◽  
pp. 3441-3452 ◽  
Author(s):  
Rebecca Eustance Kohn ◽  
Janet S. Duerr ◽  
John R. McManus ◽  
Angie Duke ◽  
Terese L. Rakow ◽  
...  

The Caenorhabditis elegans UNC-13 protein and its mammalian homologues are important for normal neurotransmitter release. We have identified a set of transcripts from the unc-13locus in C. elegans resulting from alternative splicing and apparent alternative promoters. These transcripts encode proteins that are identical in their C-terminal regions but that vary in their N-terminal regions. The most abundant protein form is localized to most or all synapses. We have analyzed the sequence alterations, immunostaining patterns, and behavioral phenotypes of 31 independentunc-13 alleles. Many of these mutations are transcript-specific; their phenotypes suggest that the different UNC-13 forms have different cellular functions. We have also isolated a deletion allele that is predicted to disrupt all UNC-13 protein products; animals homozygous for this null allele are able to complete embryogenesis and hatch, but they die as paralyzed first-stage larvae. Transgenic expression of the entire gene rescues the behavior of mutants fully; transgenic overexpression of one of the transcripts can partially compensate for the genetic loss of another. This finding suggests some degree of functional overlap of the different protein products.


2021 ◽  
Vol 43 (2) ◽  
pp. 77-78
Author(s):  
M. S. Todortseva

Taking into account the great interest in identifying the role of the nervous system in the processes of tumor growth and the insufficient study of morphological changes in the nervous apparatus of neoplasms, in our clinic (Head - Prof. AM Foy), since 1955, work has been carried out to study the effect of prolonged hyperestrogenism on the nervous apparatus of the uterus during the development of experimental fibroids in it. Experiments with long-term administration of estrogenic hormones were carried out on 120 non-castrated female guinea pigs weighing from 150.0 to 250.0, which were divided into 4 groups.


2020 ◽  
Vol 4 (1) ◽  
pp. 200-216 ◽  
Author(s):  
Emma K. Towlson ◽  
Albert-László Barabási

Synthetic lethality, the finding that the simultaneous knockout of two or more individually nonessential genes leads to cell or organism death, has offered a systematic framework to explore cellular function, and also offered therapeutic applications. Yet the concept lacks its parallel in neuroscience—a systematic knowledge base on the role of double or higher order ablations in the functioning of a neural system. Here, we use the framework of network control to systematically predict the effects of ablating neuron pairs and triplets on the gentle touch response. We find that surprisingly small sets of 58 pairs and 46 triplets can reduce muscle controllability in this context, and that these sets are localized in the nervous system in distinct groups. Further, they lead to highly specific experimentally testable predictions about mechanisms of loss of control, and which muscle cells are expected to experience this loss.


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