scholarly journals Neuronal actin dynamics, spine density and neuronal dendritic complexity are regulated by CAP2

2015 ◽  
Author(s):  
Atul Kumar ◽  
Lars Paeger ◽  
Kosmas Kosmas ◽  
Peter Kloppenburg ◽  
Angelika Noegel ◽  
...  
Keyword(s):  
Dendritic Spine ◽  
Neuronal Development ◽  
Actin Dynamics ◽  
Spine Density ◽  
Delayed Wound Healing ◽  
Actin Remodeling ◽  
Cardiovascular Defects ◽  
Dendritic Complexity

Actin remodeling is indispensable for dendritic spine development, morphology and density which signify learning, memory and motor skills. CAP2 is a regulator of actin dynamics through sequestering G-actin and severing F-actin. In a mouse model, ablation of CAP2 leads to cardiovascular defects and delayed wound healing. This report investigates the role of CAP2 in the brain using Cap2gt/gt mice. Dendritic spine density and neuronal dendritic length were altered in Cap2gt/gt. This was accompanied by increased F-actin content and F-actin accumulation in cultured Cap2gt/gt neurons. In membrane depolarization assays, Cap2gt/gt synaptosomes exhibit an impaired F/G actin ratio, indicating altered actin dynamics. We show an interaction between CAP2 and n-cofilin, presumably mediated through the C-terminal domain of CAP2 and is cofilin ser3 phosphorylation dependent. In vivo, the consequences of this interaction were altered phosphorylated cofilin levels and formation of cofilin aggregates in the neurons. Thus, our studies identify a novel role of CAP2 in neuronal development and neuronal actin dynamics.

scholarly journals Role of Numb in Dendritic Spine Development with a Cdc42 GEF Intersectin and EphB2

2006 ◽  
Vol 17 (3) ◽  
pp. 1273-1285 ◽  
Author(s):  
Takashi Nishimura ◽  
Tomoya Yamaguchi ◽  
Akinori Tokunaga ◽  
Akitoshi Hara ◽  
Tomonari Hamaguchi ◽  
...  
Keyword(s):  
Dendritic Spine ◽  
Hippocampal Neurons ◽  
Neuronal Development ◽  
System Development ◽  
Direct Interaction ◽  
Nervous System Development ◽  
Nucleotide Exchange ◽  
Spine Development

Numb has been implicated in cortical neurogenesis during nervous system development, as a result of its asymmetric partitioning and antagonizing Notch signaling. Recent studies have revealed that Numb functions in clathrin-dependent endocytosis by binding to the AP-2 complex. Numb is also expressed in postmitotic neurons and plays a role in axonal growth. However, the functions of Numb in later stages of neuronal development remain unknown. Here, we report that Numb specifically localizes to dendritic spines in cultured hippocampal neurons and is implicated in dendritic spine morphogenesis, partially through the direct interaction with intersectin, a Cdc42 guanine nucleotide exchange factor (GEF). Intersectin functions as a multidomain adaptor for proteins involved in endocytosis and cytoskeletal regulation. Numb enhanced the GEF activity of intersectin toward Cdc42 in vivo. Expression of Numb or intersectin caused the elongation of spine neck, whereas knockdown of Numb and Numb-like decreased the protrusion density and its length. Furthermore, Numb formed a complex with EphB2 receptor-type tyrosine kinase and NMDA-type glutamate receptors. Knockdown of Numb suppressed the ephrin-B1-induced spine development and maturation. These results highlight a role of Numb for dendritic spine development and synaptic functions with intersectin and EphB2.

scholarly journals In Vivo Role of Focal Adhesion Kinase in Regulating Pancreatic  -Cell Mass and Function Through Insulin Signaling, Actin Dynamics, and Granule Trafficking

Diabetes ◽  
2012 ◽  
Vol 61 (7) ◽  
pp. 1708-1718 ◽  
Author(s):  
E. P. Cai ◽  
M. Casimir ◽  
S. A. Schroer ◽  
C. T. Luk ◽  
S. Y. Shi ◽  
...  
Keyword(s):  
Focal Adhesion Kinase ◽  
Focal Adhesion ◽  
Insulin Signaling ◽  
Cell Mass ◽  
Actin Dynamics ◽  
Pancreatic Cell ◽  
And Function

scholarly journals Distal axotomy enhances retrograde presynaptic excitability onto injured pyramidal neurons via trans-synaptic signaling

2016 ◽  
Author(s):  
Tharkika Nagendran ◽  
Rylan S. Larsen ◽  
Rebecca L. Bigler ◽  
Shawn B. Frost ◽  
Benjamin D. Philpot ◽  
...  
Keyword(s):  
Dendritic Spines ◽  
Dendritic Spine ◽  
Pyramidal Neurons ◽  
Spine Density ◽  
Axon Injury ◽  
Synaptic Remodeling ◽  
Nerve Tracts ◽  
Specific Increase ◽  
Microfluidic Chambers

AbstractInjury of CNS nerve tracts remodels circuitry through dendritic spine loss and hyper-excitability, thus influencing recovery. Due to the complexity of the CNS, a mechanistic understanding of injury-induced synaptic remodeling remains unclear. Using microfluidic chambers to separate and injure distal axons, we show that axotomy causes retrograde dendritic spine loss at directly injured pyramidal neurons followed by retrograde presynaptic hyper-excitability. These remodeling events require activity at the site of injury, axon-to-soma signaling, and transcription. Similarly, directly injured corticospinal neurons in vivo also exhibit a specific increase in spiking following axon injury. Axotomy-induced hyper-excitability of cultured neurons coincides with elimination of inhibitory inputs onto injured neurons, including those formed onto dendritic spines. Netrin-1 downregulation occurs following axon injury and exogenous netrin-1 applied after injury normalizes spine density, presynaptic excitability, and inhibitory inputs at injured neurons. Our findings show that intrinsic signaling within damaged neurons regulates synaptic remodeling and involves netrin-1 signaling.

F165. Using CRISPR/Cas9-Based Epigenetic Editing to Study the Role of Schizophrenia-Related Alterations in DNA Methylation on Dendritic Spine Density

2019 ◽  
Vol 85 (10) ◽  
pp. S277
Author(s):  
Jennifer Kuflewski ◽  
Christopher Hensler ◽  
Shahwar Tariq ◽  
David Lewis ◽  
Robert Sweet ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Dendritic Spine ◽  
Spine Density ◽  
Dendritic Spine Density ◽  
Epigenetic Editing

scholarly journals TheGαoActivator Mastoparan-7 Promotes Dendritic Spine Formation in Hippocampal Neurons

2016 ◽  
Vol 2016 ◽  
pp. 1-11 ◽  
Author(s):  
Valerie T. Ramírez ◽  
Eva Ramos-Fernández ◽  
Nibaldo C. Inestrosa
Keyword(s):  
Protein Kinase ◽  
Dendritic Spine ◽  
Hippocampal Neurons ◽  
Biological Effects ◽  
Critical Role ◽  
Head Width ◽  
Dependent Manner ◽  
Spine Density ◽  
Dendritic Spine Density

Mastoparan-7 (Mas-7), an analogue of the peptide mastoparan, which is derived from wasp venom, is a direct activator ofPertussis toxin-(PTX-) sensitive G proteins. Mas-7 produces several biological effects in different cell types; however, little is known about how Mas-7 influences mature hippocampal neurons. We examined the specific role of Mas-7 in the development of dendritic spines, the sites of excitatory synaptic contact that are crucial for synaptic plasticity. We report here that exposure of hippocampal neurons to a low dose of Mas-7 increases dendritic spine density and spine head width in a time-dependent manner. Additionally, Mas-7 enhances postsynaptic density protein-95 (PSD-95) clustering in neurites and activatesGαosignaling, increasing the intracellular Ca2+concentration. To define the role of signaling intermediates, we measured the levels of phosphorylated protein kinase C (PKC), c-Jun N-terminal kinase (JNK), and calcium-calmodulin dependent protein kinase IIα(CaMKIIα) after Mas-7 treatment and determined that CaMKII activation is necessary for the Mas-7-dependent increase in dendritic spine density. Our results demonstrate a critical role forGαosubunit signaling in the regulation of synapse formation.

scholarly journals Hippocampal CA1 Pyramidal Neurons ofMecp2Mutant Mice Show a Dendritic Spine Phenotype Only in the Presymptomatic Stage

2012 ◽  
Vol 2012 ◽  
pp. 1-9 ◽  
Author(s):  
Christopher A. Chapleau ◽  
Elena Maria Boggio ◽  
Gaston Calfa ◽  
Alan K. Percy ◽  
Maurizio Giustetto ◽  
...  
Keyword(s):  
Dendritic Spines ◽  
Dendritic Spine ◽  
Pyramidal Neurons ◽  
Mutant Mice ◽  
Spine Density ◽  
Ca1 Pyramidal Neurons ◽  
Dendritic Spine Density ◽  
Presymptomatic Stage ◽  
Deficient Mice

Alterations in dendritic spines have been documented in numerous neurodevelopmental disorders, including Rett Syndrome (RTT). RTT, an X chromosome-linked disorder associated with mutations inMECP2, is the leading cause of intellectual disabilities in women. Neurons inMecp2-deficient mice show lower dendritic spine density in several brain regions. To better understand the role of MeCP2 on excitatory spine synapses, we analyzed dendritic spines of CA1 pyramidal neurons in the hippocampus ofMecp2tm1.1Jaemale mutant mice by either confocal microscopy or electron microscopy (EM). At postnatal-day 7 (P7), well before the onset of RTT-like symptoms, CA1 pyramidal neurons from mutant mice showed lower dendritic spine density than those from wildtype littermates. On the other hand, at P15 or later showing characteristic RTT-like symptoms, dendritic spine density did not differ between mutant and wildtype neurons. Consistently, stereological analyses at the EM level revealed similar densities of asymmetric spine synapses in CA1stratum radiatumof symptomatic mutant and wildtype littermates. These results raise caution regarding the use of dendritic spine density in hippocampal neurons as a phenotypic endpoint for the evaluation of therapeutic interventions in symptomaticMecp2-deficient mice. However, they underscore the potential role of MeCP2 in the maintenance of excitatory spine synapses.

ADF/n-cofilin–dependent actin turnover determines platelet formation and sizing

Blood ◽  
2010 ◽  
Vol 116 (10) ◽  
pp. 1767-1775 ◽  
Author(s):  
Markus Bender ◽  
Anita Eckly ◽  
John H. Hartwig ◽  
Margitta Elvers ◽  
Irina Pleines ◽  
...  
Keyword(s):  
Actin Filament ◽  
Molecular Mechanisms ◽  
Critical Role ◽  
Actin Dynamics ◽  
Complex Process ◽  
First Time ◽  
Late Stages ◽  
Platelet Formation

Abstract The cellular and molecular mechanisms orchestrating the complex process by which bone marrow megakaryocytes form and release platelets remain poorly understood. Mature megakaryocytes generate long cytoplasmic extensions, proplatelets, which have the capacity to generate platelets. Although microtubules are the main structural component of proplatelets and microtubule sliding is known to drive proplatelet elongation, the role of actin dynamics in the process of platelet formation has remained elusive. Here, we tailored a mouse model lacking all ADF/n-cofilin–mediated actin dynamics in megakaryocytes to specifically elucidate the role of actin filament turnover in platelet formation. We demonstrate, for the first time, that in vivo actin filament turnover plays a critical role in the late stages of platelet formation from megakaryocytes and the proper sizing of platelets in the periphery. Our results provide the genetic proof that platelet production from megakaryocytes strictly requires dynamic changes in the actin cytoskeleton.

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

scholarly journals Coronin 1A depletion restores the nuclear stability and viability of Aip1/Wdr1-deficient neutrophils

2019 ◽  
Vol 218 (10) ◽  
pp. 3258-3271
Author(s):  
Charnese Bowes ◽  
Michael Redd ◽  
Malika Yousfi ◽  
Muriel Tauzin ◽  
Emi Murayama ◽  
...  
Keyword(s):  
Cell Death ◽  
Actin Filaments ◽  
Essential Role ◽  
Actin Dynamics ◽  
Actin Binding ◽  
Zebrafish Embryos ◽  
Actomyosin Contractility ◽  
Nuclear Stability

Actin dynamics is central for cells, and especially for the fast-moving leukocytes. The severing of actin filaments is mainly achieved by cofilin, assisted by Aip1/Wdr1 and coronins. We found that in Wdr1-deficient zebrafish embryos, neutrophils display F-actin cytoplasmic aggregates and a complete spatial uncoupling of phospho-myosin from F-actin. They then undergo an unprecedented gradual disorganization of their nucleus followed by eruptive cell death. Their cofilin is mostly unphosphorylated and associated with F-actin, thus likely outcompeting myosin for F-actin binding. Myosin inhibition reproduces in WT embryos the nuclear instability and eruptive death of neutrophils seen in Wdr1-deficient embryos. Strikingly, depletion of the main coronin of leukocytes, coronin 1A, fully restores the cortical location of F-actin, nuclear integrity, viability, and mobility of Wdr1-deficient neutrophils in vivo. Our study points to an essential role of actomyosin contractility in maintaining the integrity of the nucleus of neutrophils and a new twist in the interplay of cofilin, Wdr1, and coronin in regulating F-actin dynamics.

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