scholarly journals ROCK1 and 2 differentially regulate actomyosin organization to drive cell and synaptic polarity

2015 ◽  
Vol 210 (2) ◽  
pp. 225-242 ◽  
Author(s):  
Karen A. Newell-Litwa ◽  
Mathilde Badoual ◽  
Hannelore Asmussen ◽  
Heather Patel ◽  
Leanna Whitmore ◽  
...  
Keyword(s):  
Dendritic Spines ◽  
Dendritic Spine ◽  
Actin Polymerization ◽  
Synapse Formation ◽  
Leading Edge ◽  
Actin Remodeling ◽  
Rac1 Activity ◽  
Dendritic Spine Morphology ◽  
Filament Bundles ◽  
Migratory Cells

RhoGTPases organize the actin cytoskeleton to generate diverse polarities, from front–back polarity in migrating cells to dendritic spine morphology in neurons. For example, RhoA through its effector kinase, RhoA kinase (ROCK), activates myosin II to form actomyosin filament bundles and large adhesions that locally inhibit and thereby polarize Rac1-driven actin polymerization to the protrusions of migratory fibroblasts and the head of dendritic spines. We have found that the two ROCK isoforms, ROCK1 and ROCK2, differentially regulate distinct molecular pathways downstream of RhoA, and their coordinated activities drive polarity in both cell migration and synapse formation. In particular, ROCK1 forms the stable actomyosin filament bundles that initiate front–back and dendritic spine polarity. In contrast, ROCK2 regulates contractile force and Rac1 activity at the leading edge of migratory cells and the spine head of neurons; it also specifically regulates cofilin-mediated actin remodeling that underlies the maturation of adhesions and the postsynaptic density of dendritic spines.

scholarly journals EVL and MIM/MTSS1 regulate actin cytoskeletal remodeling to promote dendritic filopodia in developing neurons

2021 ◽  
Author(s):  
Sara Shannon Parker ◽  
Kenneth Tran Ly ◽  
Adam D Grant ◽  
Ashley M Wang ◽  
James D Parker ◽  
...  
Keyword(s):  
Actin Cytoskeleton ◽  
Dendritic Spines ◽  
Actin Filaments ◽  
Actin Polymerization ◽  
Synapse Formation ◽  
Synaptic Connectivity ◽  
Critical Function ◽  
Actin Remodeling ◽  
Cytoskeletal Remodeling ◽  
Developing Neurons

Dendritic spines are the postsynaptic compartment of a functional neuronal synapse, and are critical for synaptic connectivity and plasticity. The developmental precursor to dendritic spines, dendritic filopodia, are highly motile protrusions that facilitate synapse formation by sampling the environment for suitable axon partners during development and learning. Despite the significance of the actin cytoskeleton in driving these protrusions, the actin remodeling factors involved in this process are not fully characterized. In this work, we identify a critical function for the Ena/VASP protein EVL in the regulation of dendritic filopodia. Amongst the Ena/VASP proteins, EVL is uniquely required for the characteristic morphology and dynamics of dendritic filopodia. Using a combination of genetic and optogenetic manipulations, we demonstrate that EVL promotes protrusive motility through membrane-direct actin polymerization at dendritic filopodia tips. EVL forms a complex at nascent protrusions and dendritic filopodia tips with MIM/MTSS1, an I-BAR protein recently discovered to be important for initiation of dendritic filopodia. We propose a model in which EVL cooperates with MIM to elongate and coalesce branched actin filaments, establishing the dynamic lamellipodia-like architecture of dendritic filopodia in developing neurons.

Dendritic Spine Remodeling After Spinal Cord Injury Alters Neuronal Signal Processing

2009 ◽  
Vol 102 (4) ◽  
pp. 2396-2409 ◽  
Author(s):  
Andrew M. Tan ◽  
Jin-Sung Choi ◽  
Stephen G. Waxman ◽  
Bryan C. Hains
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Synaptic Transmission ◽  
Dendritic Spines ◽  
Dendritic Spine ◽  
Nociceptive Neurons ◽  
Spine Shape ◽  
Cord Injury ◽  
Dendritic Spine Morphology ◽  
Neuronal Signal

Central sensitization, a prolonged hyperexcitability of dorsal horn nociceptive neurons, is a major contributor to abnormal pain processing after spinal cord injury (SCI). Dendritic spines are micron-sized dendrite protrusions that can regulate the efficacy of synaptic transmission. Here we used a computational approach to study whether changes in dendritic spine shape, density, and distribution can individually, or in combination, adversely modify the input–output function of a postsynaptic neuron to create a hyperexcitable neuronal state. The results demonstrate that a conversion from thin-shaped to more mature, mushroom-shaped spine structures results in enhanced synaptic transmission and fidelity, improved frequency-following ability, and reduced inhibitory gating effectiveness. Increasing the density and redistributing spines toward the soma results in a greater probability of action potential activation. Our results demonstrate that changes in dendritic spine morphology, documented in previous studies on spinal cord injury, contribute to the generation of pain following SCI.

scholarly journals Analysis of the Actin–Myosin II System in Fish Epidermal Keratocytes: Mechanism of Cell Body Translocation

1997 ◽  
Vol 139 (2) ◽  
pp. 397-415 ◽  
Author(s):  
Tatyana M. Svitkina ◽  
Alexander B. Verkhovsky ◽  
Kyle M. McQuade ◽  
Gary G. Borisy
Keyword(s):  
Cell Body ◽  
Actin Filaments ◽  
Actin Polymerization ◽  
Myosin Ii ◽  
Leading Edge ◽  
Time Lapse ◽  
Supramolecular Organization ◽  
Retrograde Flow ◽  
Body Boundary ◽  
Filament Bundles

While the protrusive event of cell locomotion is thought to be driven by actin polymerization, the mechanism of forward translocation of the cell body is unclear. To elucidate the mechanism of cell body translocation, we analyzed the supramolecular organization of the actin–myosin II system and the dynamics of myosin II in fish epidermal keratocytes. In lamellipodia, long actin filaments formed dense networks with numerous free ends in a brushlike manner near the leading edge. Shorter actin filaments often formed T junctions with longer filaments in the brushlike area, suggesting that new filaments could be nucleated at sides of preexisting filaments or linked to them immediately after nucleation. The polarity of actin filaments was almost uniform, with barbed ends forward throughout most of the lamellipodia but mixed in arc-shaped filament bundles at the lamellipodial/cell body boundary. Myosin II formed discrete clusters of bipolar minifilaments in lamellipodia that increased in size and density towards the cell body boundary and colocalized with actin in boundary bundles. Time-lapse observation demonstrated that myosin clusters appeared in the lamellipodia and remained stationary with respect to the substratum in locomoting cells, but they exhibited retrograde flow in cells tethered in epithelioid colonies. Consequently, both in locomoting and stationary cells, myosin clusters approached the cell body boundary, where they became compressed and aligned, resulting in the formation of boundary bundles. In locomoting cells, the compression was associated with forward displacement of myosin features. These data are not consistent with either sarcomeric or polarized transport mechanisms of cell body translocation. We propose that the forward translocation of the cell body and retrograde flow in the lamellipodia are both driven by contraction of an actin–myosin network in the lamellipodial/cell body transition zone.

scholarly journals Biophysical model of the role of actin remodeling on dendritic spine morphology

PLoS ONE ◽  
2017 ◽  
Vol 12 (2) ◽  
pp. e0170113 ◽  
Author(s):  
C. A. Miermans ◽  
R. P. T. Kusters ◽  
C. C. Hoogenraad ◽  
C. Storm
Keyword(s):  
Dendritic Spine ◽  
Biophysical Model ◽  
Actin Remodeling ◽  
Spine Morphology ◽  
Dendritic Spine Morphology

Toward a Brain-Inspired Developmental Neural Network Based on Dendritic Spine Dynamics

2021 ◽  
pp. 1-18
Author(s):  
Feifei Zhao ◽  
Yi Zeng ◽  
Jun Bai
Keyword(s):  
Neural Network ◽  
Dendritic Spines ◽  
Dendritic Spine ◽  
Synapse Formation ◽  
Dynamic Structure ◽  
Classification Performance ◽  
Synaptic Activity ◽  
Data Sets ◽  
Spine Density ◽  
Spine Dynamics

Abstract Neural networks with a large number of parameters are prone to overfitting problems when trained on a relatively small training set. Introducing weight penalties of regularization is a promising technique for solving this problem. Taking inspiration from the dynamic plasticity of dendritic spines, which plays an important role in the maintenance of memory, this letter proposes a brain-inspired developmental neural network based on dendritic spine dynamics (BDNN-dsd). The dynamic structure changes of dendritic spines include appearing, enlarging, shrinking, and disappearing. Such spine plasticity depends on synaptic activity and can be modulated by experiences—in particular, long-lasting synaptic enhancement/suppression (LTP/LTD), coupled with synapse formation (or enlargement)/elimination (or shrinkage), respectively. Subsequently, spine density characterizes an approximate estimate of the total number of synapses between neurons. Motivated by this, we constrain the weight to a tunable bound that can be adaptively modulated based on synaptic activity. Dynamic weight bound could limit the relatively redundant synapses and facilitate the contributing synapses. Extensive experiments demonstrate the effectiveness of our method on classification tasks of different complexity with the MNIST, Fashion MNIST, and CIFAR-10 data sets. Furthermore, compared to dropout and L2 regularization algorithms, our method can improve the network convergence rate and classification performance even for a compact network.

scholarly journals nArgBP2 regulates excitatory synapse formation by controlling dendritic spine morphology

2016 ◽  
Vol 113 (24) ◽  
pp. 6749-6754 ◽  
Author(s):  
Sang-Eun Lee ◽  
Yoonju Kim ◽  
Jeong-Kyu Han ◽  
Hoyong Park ◽  
Unghwi Lee ◽  
...  
Keyword(s):  
Bipolar Disorder ◽  
Dendritic Spine ◽  
Synapse Formation ◽  
Scaffolding Protein ◽  
Glutamatergic Synapses ◽  
Spine Morphology ◽  
Homologous Protein ◽  
Dendritic Spine Morphology ◽  
P21 Activated Kinase ◽  
Cytoskeleton Dynamics

Neural Abelson-related gene-binding protein 2 (nArgBP2) was originally identified as a protein that directly interacts with synapse-associated protein 90/postsynaptic density protein 95-associated protein 3 (SAPAP3), a postsynaptic scaffolding protein critical for the assembly of glutamatergic synapses. Although genetic deletion of nArgBP2 in mice leads to manic/bipolar-like behaviors resembling many aspects of symptoms in patients with bipolar disorder, the actual function of nArgBP2 at the synapse is completely unknown. Here, we found that the knockdown (KD) of nArgBP2 by specific small hairpin RNAs (shRNAs) resulted in a dramatic change in dendritic spine morphology. Reintroducing shRNA-resistant nArgBP2 reversed these defects. In particular, nArgBP2 KD impaired spine-synapse formation such that excitatory synapses terminated mostly at dendritic shafts instead of spine heads in spiny neurons, although inhibitory synapse formation was not affected. nArgBP2 KD further caused a marked increase of actin cytoskeleton dynamics in spines, which was associated with increased Wiskott–Aldrich syndrome protein-family verprolin homologous protein 1 (WAVE1)/p21-activated kinase (PAK) phosphorylation and reduced activity of cofilin. These effects of nArgBP2 KD in spines were rescued by inhibiting PAK or activating cofilin combined with sequestration of WAVE. Together, our results suggest that nArgBP2 functions to regulate spine morphogenesis and subsequent spine-synapse formation at glutamatergic synapses. They also raise the possibility that the aberrant regulation of synaptic actin filaments caused by reduced nArgBP2 expression may contribute to the manifestation of the synaptic dysfunction observed in manic/bipolar disorder.

Phosphorylation of WAVE1 regulates actin polymerization and dendritic spine morphology

Nature ◽  
2006 ◽  
Vol 442 (7104) ◽  
pp. 814-817 ◽  
Author(s):  
Yong Kim ◽  
Jee Young Sung ◽  
Ilaria Ceglia ◽  
Ko-Woon Lee ◽  
Jung-Hyuck Ahn ◽  
...  
Keyword(s):  
Dendritic Spine ◽  
Actin Polymerization ◽  
Spine Morphology ◽  
Dendritic Spine Morphology
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