scholarly journals Profilin2 regulates actin rod assembly in neuronal cells

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Lisa Marie Walter ◽  
Sebastian Rademacher ◽  
Andreas Pich ◽  
Peter Claus
Keyword(s):  
Neurological Disorders ◽  
Atp Hydrolysis ◽  
Muscular Atrophy ◽  
Actin Dynamics ◽  
Cell Culture Model ◽  
Cellular Functions ◽  
Cytoplasmic Actin ◽  
Culture Model ◽  
Cellular Pathways ◽  
Cofilin Rods

AbstractNuclear and cytoplasmic actin-cofilin rods are formed transiently under stress conditions to reduce actin filament turnover and ATP hydrolysis. The persistence of these structures has been implicated in disease pathology of several neurological disorders. Recently, the presence of actin rods has been discovered in Spinal Muscular Atrophy (SMA), a neurodegenerative disease affecting predominantly motoneurons leading to muscle weakness and atrophy. This finding underlined the importance of dysregulated actin dynamics in motoneuron loss in SMA. In this study, we characterized actin rods formed in a SMA cell culture model analyzing their composition by LC–MS-based proteomics. Besides actin and cofilin, we identified proteins involved in processes such as ubiquitination, translation or protein folding to be bound to actin rods. This suggests their sequestration to actin rods, thus impairing important cellular functions. Moreover, we showed the involvement of the cytoskeletal protein profilin2 and its upstream effectors RhoA/ROCK in actin rod assembly in SMA. These findings implicate that the formation of actin rods exerts detrimental effects on motoneuron homeostasis by affecting actin dynamics and disturbing essential cellular pathways.

scholarly journals Profilin Isoforms in Health and Disease – All the Same but Different

2021 ◽  
Vol 9 ◽  
Author(s):  
Kai Murk ◽  
Marta Ornaghi ◽  
Juliane Schiweck
Keyword(s):  
Actin Polymerization ◽  
Muscular Atrophy ◽  
Fragile X ◽  
Neurological Diseases ◽  
Actin Dynamics ◽  
Actin Binding ◽  
Cellular Functions ◽  
Numerous Cell ◽  
The Central Nervous System ◽  
Number Of Publications

Profilins are small actin binding proteins, which are structurally conserved throughout evolution. They are probably best known to promote and direct actin polymerization. However, they also participate in numerous cell biological processes beyond the roles typically ascribed to the actin cytoskeleton. Moreover, most complex organisms express several profilin isoforms. Their cellular functions are far from being understood, whereas a growing number of publications indicate that profilin isoforms are involved in the pathogenesis of various diseases. In this review, we will provide an overview of the profilin family and “typical” profilin properties including the control of actin dynamics. We will then discuss the profilin isoforms of higher animals in detail. In terms of cellular functions, we will focus on the role of Profilin 1 (PFN1) and Profilin 2a (PFN2a), which are co-expressed in the central nervous system. Finally, we will discuss recent findings that link PFN1 and PFN2a to neurological diseases, such as amyotrophic lateral sclerosis (ALS), Fragile X syndrome (FXS), Huntington’s disease and spinal muscular atrophy (SMA).

scholarly journals Formation of Cytoplasmic Actin-Cofilin Rods is Triggered by Metabolic Stress and Changes in Cellular pH

2021 ◽  
Vol 9 ◽  
Author(s):  
Hellen C. Ishikawa-Ankerhold ◽  
Sophie Kurzbach ◽  
Arzu S. Kinali ◽  
Annette Müller-Taubenberger
Keyword(s):  
Metabolic Stress ◽  
Nemaline Myopathy ◽  
Actin Dynamics ◽  
Cellular Energy ◽  
Cell Functions ◽  
Cytoplasmic Actin ◽  
Pathological Conditions ◽  
Local Reduction ◽  
Cofilin Rods ◽  
Lateral Sclerosis

Actin dynamics plays a crucial role in regulating essential cell functions and thereby is largely responsible to a considerable extent for cellular energy consumption. Certain pathological conditions in humans, like neurological disorders such as Alzheimer’s disease or amyotrophic lateral sclerosis (ALS) as well as variants of nemaline myopathy are associated with cytoskeletal abnormalities, so-called actin-cofilin rods. Actin-cofilin rods are aggregates consisting mainly of actin and cofilin, which are formed as a result of cellular stress and thereby help to ensure the survival of cells under unfavorable conditions. We have used Dictyostelium discoideum, an established model system for cytoskeletal research to study formation and principles of cytoplasmic actin rod assembly in response to energy depletion. Experimentally, depletion of ATP was provoked by addition of either sodium azide, dinitrophenol, or 2-deoxy-glucose, and the formation of rod assembly was recorded by live-cell imaging. Furthermore, we show that hyperosmotic shock induces actin-cofilin rods, and that a drop in the intracellular pH accompanies this condition. Our data reveal that acidification of the cytoplasm can induce the formation of actin-cofilin rods to varying degrees and suggest that a local reduction in cellular pH may be a cause for the formation of cytoplasmic rods. We hypothesize that local phase separation mechanistically triggers the assembly of actin-cofilin rods and thereby influences the material properties of actin structures.

1120: Citrate and Vitamin E Blunt the SWL-Induced Free Radical Surge in an In-Vitro MDCK Cell Culture Model

2004 ◽  
Vol 171 (4S) ◽  
pp. 295-295
Author(s):  
Fernando C. Delvecchio ◽  
Ricardo M. Brizuela ◽  
Karen J. Byer ◽  
W. Patrick Springhart ◽  
Saeed R. Khan ◽  
...  
Keyword(s):  
Cell Culture ◽  
Free Radical ◽  
Vitamin E ◽  
Mdck Cell ◽  
Cell Culture Model ◽  
Culture Model
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