Nestin Is Not Essential for Development of the CNS But Required for Dispersion of Acetylcholine Receptor Clusters at the Area of Neuromuscular Junctions

Mohseni, Paria; Sung, Hoon‐Ki; Murphy, Anna V.; Laliberté, Christine; Pallari, Hanna Mari; Henkelman, Mark; Georgiou, John; Xie, Gang; Quaggin, Susan E.; Thorner, Paul; Eriksson, John E.; Nagy, András

doi:10.1523/jneurosci.4396-10.2011

Cited by 45 publications

(60 citation statements)

References 36 publications

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“…We hypothesised that nestin could affect FAK directly, in the same way that synemin, an intermediate filament protein that is structurally similar to nestin, binds to zyxin, thereby affecting its localisation at focal adhesions Sun et al, 2010). Nestin has been shown to have the propensity to act as a cytoskeletal signalling regulator, as it regulates Cdk5, with consequences for Cdk5 activation and localisation in neural progenitor cells, myoblasts and at the neuromuscular junctions (Mohseni et al, 2011;Pallari et al, 2011;Sahlgren et al, 2006;Yang et al, 2011). In agreement with these reports, our current results suggest that nestin also has the capacity to act as a cytoskeletal regulator of FAK organisation and activity.…”

Section: Discussionmentioning

confidence: 99%

Nestin regulates prostate cancer cell invasion by influencing FAK and integrin localisation and functions

Hyder

Lazaro

Pylvänäinen

et al. 2014

Journal of Cell Science

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BSTRACTNestin, an intermediate filament protein and marker of undifferentiated cells, is expressed in several cancers. Nestin is important for neuronal survival and is a regulator of myogenesis but its function in malignancy is ambiguous. We show that nestin downregulation leads to a redistribution of phosphorylated focal adhesion kinase (pFAK, also known as PTK2) to focal adhesions and alterations in focal adhesion turnover. Nestin downregulation also leads to an increase in the protein levels of integrin a5b1 at the cell membrane, activation of integrin b1 and an increase in integrin clustering. These effects have striking consequences for cell invasion, as nestin downregulation leads to a significant increase in pFAK-and integrin-dependent matrix degradation and cell invasion. Our results indicate that nestin regulates the localisation and functions of FAK and integrin. Because nestin has been shown to be prevalent in a number of specific cancers, our observations have broad ramifications for the roles of nestin in malignant transformation.

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Section: Discussionmentioning

confidence: 99%

Nestin regulates prostate cancer cell invasion by influencing FAK and integrin localisation and functions

Hyder

Lazaro

Pylvänäinen

et al. 2014

Journal of Cell Science

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“…Mice ( Nes −/− and wild‐type) were from a C57BL/6‐129Sv mixed genetic background. The viable and fertile mice were genotyped by PCR as previously described . All animals were kept in the barrier facility of the University of Gothenburg and experiments were conducted according to protocols approved by the Ethics Committee.…”

Section: Methodsmentioning

confidence: 99%

Nestin affects fusion pore dynamics in mouse astrocytes

et al. 2019

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Aim Astrocytes play a homeostatic role in the central nervous system and influence numerous aspects of neurophysiology via intracellular trafficking of vesicles. Intermediate filaments (IFs), also known as nanofilaments, regulate a number of cellular processes including organelle trafficking and adult hippocampal neurogenesis. We have recently demonstrated that the IF protein nestin, a marker of neural stem cells and immature and reactive astrocytes, is also expressed in some astrocytes in the unchallenged hippocampus and regulates neurogenesis through Notch signalling from astrocytes to neural stem cells, possibly via altered trafficking of vesicles containing the Notch ligand Jagged‐1. Methods We thus investigated whether nestin affects vesicle dynamics in astrocytes by examining single vesicle interactions with the plasmalemma and vesicle trafficking with high‐resolution cell‐attached membrane capacitance measurements and confocal microscopy. We used cell cultures of astrocytes from nestin‐deficient (Nes−/−) and wild‐type (wt) mice, and fluorescent dextran and Fluo‐2 to examine vesicle mobility and intracellular Ca2+ concentration respectively. Results Nes−/− astrocytes exhibited altered sizes of vesicles undergoing full fission and transient fusion, altered vesicle fusion pore geometry and kinetics, decreased spontaneous vesicle mobility and altered ATP‐evoked mobility. Purinergic stimulation evoked Ca2+ signalling that was slightly attenuated in Nes−/− astrocytes, which exhibited more oscillatory Ca2+ responses than wt astrocytes. Conclusion These results demonstrate at the single vesicle level that nestin regulates vesicle interactions with the plasmalemma and vesicle trafficking, indicating its potential role in astrocyte vesicle‐based communication.

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“…Prolonged Cdk5 activation, which is enabled after its dissociation from dissasembled phospho-nestin, is required for acetylcholine (Ach)-induced dispersal of Ach receptor (AchR) clusters 71 . Similar to Cdk5-null mice, nestin-null mice exhibit impaired motor coordination and an increased number of AchR clusters in NMJ areas 72 . These studies demonstrate the importance of IF phosphorylation during neuromuscular development.…”

Section: If Phosphorylation: Multifunctional Ptmmentioning

confidence: 95%

Post-translational modifications of intermediate filament proteins: mechanisms and functions

Snider

Omary

2014

Nat Rev Mol Cell Biol

434

426

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Preface Intermediate filaments (IFs) are cytoskeletal and nucleoskeletal structures that provide mechanical and stress-coping resilience to cells, contribute to subcellular and tissue-specific biological functions, and facilitate intracellular communication. IF proteins, including nuclear lamins and cytoplasmic keratins, vimentin, desmin, neurofilaments, and glial fibrillary acidic protein, undergo various functionally important post-translational modifications (PTMs). Proteomic advances highlight the enormous complexity of IF PTMs, which include phosphorylation, glycosylation, sumoylation, acetylation, and prenylation, as well as their ability to regulate IF proteins, and are likely to reveal novel modifications. We would like to keep the original statement, since the revised version seems to imply that proteomic advances provide insight into the ability of PTMs to regulate IF proteins, which is not the case. Future studies will need to characterize their on–off mechanisms, cross-talk, and utility as biomarkers and targets for diseases involving the IF cytoskeleton.

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Nestin Is Not Essential for Development of the CNS But Required for Dispersion of Acetylcholine Receptor Clusters at the Area of Neuromuscular Junctions

Cited by 45 publications

References 36 publications

Nestin regulates prostate cancer cell invasion by influencing FAK and integrin localisation and functions

Nestin regulates prostate cancer cell invasion by influencing FAK and integrin localisation and functions

Nestin affects fusion pore dynamics in mouse astrocytes

Post-translational modifications of intermediate filament proteins: mechanisms and functions

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