Positioning of the Centrosome and Golgi Complex

Orlofsky, Amos

doi:10.1007/978-3-030-23173-6_7

Cited by 8 publications

(9 citation statements)

References 364 publications

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“…The missplicing of a significant number of transcripts coding for tubulin-binding proteins and regulators of microtubule dynamics in DMSXL astrocytes may therefore contribute to the misorientation of the microtubule-organizing center (MTOC) and the erratic migration during the wound healing assay. Changes in the activity of CLASP1, for example, were shown to cause random cell movement in culture, similar to those detected in DMSXL astrocytes 57 ; SORBS1 regulates cell adhesion, spreading, and migration 58 ; and NUMA1 controls cell polarity, and the dynamics of microtubules 59 . The uncontrolled cell movement and increased speed of DMSXL astrocytes, may also result from the low number of stable focal adhesions, which under normal conditions tend to inhibit cell migration 60 .…”

Section: Discussionmentioning

confidence: 57%

Myotonic dystrophy RNA toxicity alters morphology, adhesion and migration of mouse and human astrocytes

et al. 2022

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Brain dysfunction in myotonic dystrophy type 1 (DM1), the prototype of toxic RNA disorders, has been mainly attributed to neuronal RNA misprocessing, while little attention has been given to non-neuronal brain cells. Here, using a transgenic mouse model of DM1 that expresses mutant RNA in various brain cell types (neurons, astroglia, and oligodendroglia), we demonstrate that astrocytes exhibit impaired ramification and polarization in vivo and defects in adhesion, spreading, and migration. RNA-dependent toxicity and phenotypes are also found in human transfected glial cells. In line with the cell phenotypes, molecular analyses reveal extensive expression and accumulation of toxic RNA in astrocytes, which result in RNA spliceopathy that is more severe than in neurons. Astrocyte missplicing affects primarily transcripts that regulate cell adhesion, cytoskeleton, and morphogenesis, and it is confirmed in human brain tissue. Our findings demonstrate that DM1 impacts astrocyte cell biology, possibly compromising their support and regulation of synaptic function.

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Section: Discussionmentioning

confidence: 57%

Myotonic dystrophy RNA toxicity alters morphology, adhesion and migration of mouse and human astrocytes

et al. 2022

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“…The Golgi and the centrosome are spatially and functionally connected in most cells [151,[193][194][195]. During cell polarization and cell migration, physical contact between the Golgi and the centrosome allows for a coordinated re-localization of both structures, e.g., towards the leading edge of the migrating cell.…”

Section: Golgi Organization and Mtoc Formation Are Coordinated Processesmentioning

confidence: 99%

Microtubule Organization in Striated Muscle Cells

Becker

Leone

Engel

2020

Cells

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Distinctly organized microtubule networks contribute to the function of differentiated cell types such as neurons, epithelial cells, skeletal myotubes, and cardiomyocytes. In striated (i.e., skeletal and cardiac) muscle cells, the nuclear envelope acts as the dominant microtubule-organizing center (MTOC) and the function of the centrosome—the canonical MTOC of mammalian cells—is attenuated, a common feature of differentiated cell types. We summarize the mechanisms known to underlie MTOC formation at the nuclear envelope, discuss the significance of the nuclear envelope MTOC for muscle function and cell cycle progression, and outline potential mechanisms of centrosome attenuation.

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“…The missplicing of a signi cant number of transcripts coding for tubulin-binding proteins and regulators of microtubule dynamics in DMSXL astrocytes may therefore contribute to the misorientation of the microtubule-organizing center (MTOC) and the erratic migration during the wound healing assay. Changes in the activity of CLASP1, for example, were shown to cause random cell movement in culture, similar to those detected in DMSXL astrocytes 40 ; SORBS1 regulates cell adhesion, spreading and migration 41 ; and NUMA1 controls cell polarity and the dynamics of microtubules 42 . The uncontrolled cell movement and increase speed of DMSXL astrocytes, may also result from the low number of stable focal adhesions, which under normal conditions tend to inhibit cell migration 43 .…”

Section: Discussionmentioning

confidence: 57%

Myotonic dystrophy RNA toxicity alters morphology, adhesion and migration of mouse and human astrocytes

Dincã

González-Barriga

Sicot

et al. 2021

Preprint

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Brain dysfunction in myotonic dystrophy type 1 (DM1), the prototype of toxic RNA disorders, has been mainly attributed to neuronal RNA misprocessing, while little attention has been given to non-neuronal brain cells. Using a transgenic mouse model of DM1 that expresses mutant RNA in various brain cell types, we demonstrate that astrocytes exhibit impaired ramification and polarization in vivo and defects in adhesion, spreading and migration. RNA-dependent toxicity and phenotypes was also found in human transfected glial cells. In line with the cell phenotypes, molecular analyses revealed extensive expression and accumulation of toxic RNA in astrocytes, which resulted in RNA spliceopathy that was remarkably more severe than in neurons. Astrocyte missplicing affected primarily transcripts that regulate cell adhesion, cytoskeleton and morphogenesis, and it was confirmed in human brain tissue. We demonstrate for the first time that DM1 impacts astrocyte cell biology, possibly compromising their support and regulation of synaptic function.

show abstract

Positioning of the Centrosome and Golgi Complex

Cited by 8 publications

References 364 publications

Myotonic dystrophy RNA toxicity alters morphology, adhesion and migration of mouse and human astrocytes

Myotonic dystrophy RNA toxicity alters morphology, adhesion and migration of mouse and human astrocytes

Microtubule Organization in Striated Muscle Cells

Myotonic dystrophy RNA toxicity alters morphology, adhesion and migration of mouse and human astrocytes

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