scholarly journals Calcineurin-dependent cofilin activation and increased retrograde actin flow drive 5-HT–dependent neurite outgrowth in Aplysia bag cell neurons

2012 ◽  
Vol 23 (24) ◽  
pp. 4833-4848 ◽  
Author(s):  
Xiao-Feng Zhang ◽  
Callen Hyland ◽  
David Van Goor ◽  
Paul Forscher
Keyword(s):  
Neurite Outgrowth ◽  
Growth Cone ◽  
Network Flow ◽  
Calcineurin Inhibitors ◽  
Actin Network ◽  
Flow Acceleration ◽  
Threefold Increase ◽  
Intracellular Ca ◽  
P Domain ◽  
Bag Cell Neurons

Neurite outgrowth in response to soluble growth factors often involves changes in intracellular Ca2+; however, mechanistic roles for Ca2+ in controlling the underlying dynamic cytoskeletal processes have remained enigmatic. Bag cell neurons exposed to serotonin (5-hydroxytryptamine [5-HT]) respond with a threefold increase in neurite outgrowth rates. Outgrowth depends on phospholipase C (PLC) → inositol trisphosphate → Ca2+ → calcineurin signaling and is accompanied by increased rates of retrograde actin network flow in the growth cone P domain. Calcineurin inhibitors had no effect on Ca2+ release or basal levels of retrograde actin flow; however, they completely suppressed 5-HT–dependent outgrowth and F-actin flow acceleration. 5-HT treatments were accompanied by calcineurin-dependent increases in cofilin activity in the growth cone P domain. 5-HT effects were mimicked by direct activation of PLC, suggesting that increased actin network treadmilling may be a widespread mechanism for promoting neurite outgrowth in response to neurotrophic factors.

scholarly journals Regulation of axon growth by myosin II–dependent mechanocatalysis of cofilin activity

2019 ◽  
Vol 218 (7) ◽  
pp. 2329-2349 ◽  
Author(s):  
Xiao-Feng Zhang ◽  
Visar Ajeti ◽  
Nicole Tsai ◽  
Arash Fereydooni ◽  
William Burns ◽  
...  
Keyword(s):  
Growth Cone ◽  
Network Flow ◽  
Myosin Ii ◽  
Point Contact ◽  
Traction Force ◽  
Axon Growth ◽  
Network Density ◽  
Actin Network ◽  
Growth Responses ◽  
Contact Density

Serotonin (5-HT) is known to increase the rate of growth cone advance via cofilin-dependent increases in retrograde actin network flow and nonmuscle myosin II activity. We report that myosin II activity is regulated by PKC during 5-HT responses and that PKC activity is necessary for increases in traction force normally associated with these growth responses. 5-HT simultaneously induces cofilin-dependent decreases in actin network density and PKC-dependent increases in point contact density. These reciprocal effects facilitate increases in traction force production in domains exhibiting decreased actin network density. Interestingly, when PKC activity was up-regulated, 5-HT treatments resulted in myosin II hyperactivation accompanied by catastrophic cofilin-dependent decreases in actin filament density, sudden decreases in traction force, and neurite retraction. These results reveal a synergistic relationship between cofilin and myosin II that is spatiotemporally regulated in the growth cone via mechanocatalytic effects to modulate neurite growth.

Mitochondrial Ca2+ Activates a Cation Current in Aplysia Bag Cell Neurons

2010 ◽  
Vol 103 (3) ◽  
pp. 1543-1556 ◽  
Author(s):  
Charlene M. Hickey ◽  
Julia E. Geiger ◽  
Chris J. Groten ◽  
Neil S. Magoski
Keyword(s):  
Endoplasmic Reticulum ◽  
Ion Channels ◽  
Time Course ◽  
Reversal Potential ◽  
Neuroendocrine Cells ◽  
Dependent Manner ◽  
Inward Current ◽  
Cation Current ◽  
Intracellular Ca ◽  
Bag Cell Neurons

Ion channels may be gated by Ca2+ entering from the extracellular space or released from intracellular stores—typically the endoplasmic reticulum. The present study examines how Ca2+ impacts ion channels in the bag cell neurons of Aplysia californica. These neuroendocrine cells trigger ovulation through an afterdischarge involving Ca2+ influx from Ca2+ channels and Ca2+ release from both the mitochondria and endoplasmic reticulum. Liberating mitochondrial Ca2+ with the protonophore, carbonyl cyanide-4-trifluoromethoxyphenyl-hydrazone (FCCP), depolarized bag cell neurons, whereas depleting endoplasmic reticulum Ca2+ with the Ca2+-ATPase inhibitor, cyclopiazonic acid, did not. In a concentration-dependent manner, FCCP elicited an inward current associated with an increase in conductance and a linear current/voltage relationship that reversed near −40 mV. The reversal potential was unaffected by changing intracellular Cl−, but left-shifted when extracellular Ca2+ was removed and right-shifted when intracellular K+ was decreased. Strong buffering of intracellular Ca2+ decreased the current, although the response was not altered by blocking Ca2+-dependent proteases. Furthermore, fura imaging demonstrated that FCCP elevated intracellular Ca2+ with a time course similar to the current itself. Inhibiting either the V-type H+-ATPase or the ATP synthetase failed to produce a current, ruling out acidic Ca2+ stores or disruption of ATP production as mechanisms for the FCCP response. Similarly, any involvement of reactive oxygen species potentially produced by mitochondrial depolarization was mitigated by the fact that dialysis with xanthine/xanthine oxidase did not evoke an inward current. However, both the FCCP-induced current and Ca2+ elevation were diminished by disabling the mitochondrial permeability transition pore with the alkylating agent, N-ethylmaleimide. The data suggest that mitochondrial Ca2+ gates a voltage-independent, nonselective cation current with the potential to drive the afterdischarge and contribute to reproduction. Employing Ca2+ from mitochondria, rather than the more common endoplasmic reticulum, represents a diversification of the mechanisms that influence neuronal activity.

scholarly journals Evidence that calcium may control neurite outgrowth by regulating the stability of actin filaments.

1989 ◽  
Vol 109 (3) ◽  
pp. 1229-1243 ◽  
Author(s):  
K L Lankford ◽  
P C Letourneau
Keyword(s):  
Neurite Outgrowth ◽  
Growth Cone ◽  
Actin Filaments ◽  
Monovalent Cation ◽  
Stabilizing Agent ◽  
Growth Cone Collapse ◽  
Neurite Retraction ◽  
Calcium Removal ◽  
The Stability ◽  
Triton X

We investigated the effects of calcium removal and calcium ionophores on the behavior and ultrastructure of cultured chick dorsal root ganglia (DRG) neurons to identify possible mechanisms by which calcium might regulate neurite outgrowth. Both calcium removal and the addition of calcium ionophores A23187 or ionomycin blocked outgrowth in previously elongating neurites, although in the case of calcium ionophores, changes in growth cone shape and retraction of neurites were also observed. Treatment with calcium ionophores significantly increased growth cone calcium. The ability of the microtubule stabilizing agent taxol to block A23187-induced neurite retraction and the ability of the actin stabilizing agent phalloidin to reverse both A23187-induced growth cone collapse and neurite retraction suggested that calcium acted on the cytoskeleton. Whole mount electron micrographs revealed an apparent disruption of actin filaments in the periphery (but not filopodia) of growth cones that were exposed to calcium ionophores in medium with normal calcium concentrations. This effect was not seen in cells treated with calcium ionophores in calcium-free medium or cells treated with the monovalent cation ionophore monensin, indicating that these effects were calcium specific. Ultrastructure of Triton X-100 extracted whole mounts further indicated that both microtubules and microfilaments may be more stable or extraction resistant after treatments which lower intracellular calcium. Taken together, the data suggest that calcium may control neurite elongation at least in part by regulating actin filament stability, and support a model for neurite outgrowth involving a balance between assembly and disassembly of the cytoskeleton.

scholarly journals Cell adhesion molecules NgCAM and axonin-1 form heterodimers in the neuronal membrane and cooperate in neurite outgrowth promotion.

1996 ◽  
Vol 135 (6) ◽  
pp. 1593-1607 ◽  
Author(s):  
A Buchstaller ◽  
S Kunz ◽  
P Berger ◽  
B Kunz ◽  
U Ziegler ◽  
...  
Keyword(s):  
Cell Adhesion ◽  
Neurite Outgrowth ◽  
Dorsal Root Ganglia ◽  
Growth Cone ◽  
Dorsal Root ◽  
Cell Aggregation ◽  
Neuronal Membrane ◽  
Direct Binding ◽  
Dorsal Root Ganglia Neurons ◽  
Cis Interaction

The axonal surface glycoproteins neuronglia cell adhesion molecule (NgCAM) and axonin-1 promote cell-cell adhesion, neurite outgrowth and fasciculation, and are involved in growth cone guidance. A direct binding between NgCAM and axonin-1 has been demonstrated using isolated molecules conjugated to the surface of fluorescent microspheres. By expressing NgCAM and axonin-1 in myeloma cells and performing cell aggregation assays, we found that NgCAM and axonin-1 cannot bind when present on the surface of different cells. In contrast, the cocapping of axonin-1 upon antibody-induced capping of NgCAM on the surface of CV-1 cells coexpressing NgCAM and axonin-1 and the selective chemical cross-linking of the two molecules in low density cultures of dorsal root ganglia neurons indicated a specific and direct binding of axonin-1 and Ng-CAM in the plane of the same membrane. Suppression of the axonin-1 translation by antisense oligonucleotides prevented neurite outgrowth in dissociated dorsal root ganglia neurons cultured on an NgCAM substratum, indicating that neurite outgrowth on NgCAM substratum requires axonin-1. Based on these and previous results, which implicated NgCAM as the neuronal receptor involved in neurite outgrowth on NgCAM substratum, we concluded that neurite outgrowth on an NgCAM substratum depends on two essential interactions of growth cone NgCAM: a trans-interaction with substratum NgCAM and a cis-interaction with axonin-1 residing in the same growth cone membrane.

scholarly journals Nogo-A Beyond the RhoA/ROCK Pathway – Novel Components of Intracellular Nogo-A Signaling Cascades

2020 ◽  
Author(s):  
Martina A. Maibach ◽  
Ester Piovesana ◽  
Julia Kaiser ◽  
Mea M. Holm ◽  
Zorica Risic ◽  
...  
Keyword(s):  
Neurite Outgrowth ◽  
Growth Cone ◽  
Signaling Cascades ◽  
Growth Cone Collapse ◽  
Neurite Retraction ◽  
Downstream Effector ◽  
Fibre Growth ◽  
Growth Promoting

AbstractNogo-A is a well-characterized myelin-associated membrane protein that restricts fibre growth and the regenerative capacity of the adult central nervous system after injury. To date Nogo-A post-receptor signalling pathway research focused on the RhoA/ROCK cascade, which can lead to growth cone collapse and neurite retraction. Much less is known about continued intracellular Nogo-A signalling mediating long-term neurite outgrowth inhibition resulting from transcriptional and translational changes. Here, we propose a simple but highly reproducible in vitro assay to study Nogo-A related signaling and neurite outgrowth inhibition in general. Furthermore, we identified ERK1/2 as downstream effector of Nogo-A, partially mediating its neurite outgrowth inhibition. We describe ERK1/2 dependent changes of translational events such as elevation of RhoA levels within the growth cone, which may potentiate the cells’ responses to Nogo-A. We also observed Nogo-A dependent upregulation of the JAK/STAT pathway inhibitors SOCS3 and KLF4 and downregulation of insulin mediated phosphorylation of AKT, indicating direct negative crosstalk between Nogo-A signalling and the growth promoting JAK/STAT and AKT/mTORC1 pathways.

scholarly journals Extracellular Pgk1 enhances neurite outgrowth of motoneurons through Nogo66-independent targeting of NogoA

2019 ◽  
Author(s):  
Cheng Yung Lin ◽  
Chia Lun Wu ◽  
Kok Zhi Lee ◽  
You Jei Chen ◽  
Po Hsiang Zhang ◽  
...  
Keyword(s):  
Amyotrophic Lateral Sclerosis ◽  
Mouse Model ◽  
Neurite Outgrowth ◽  
Growth Cone ◽  
Knockout Mice ◽  
Phosphoglycerate Kinase ◽  
Muscle Cells ◽  
Growth Cone Collapse ◽  
Nogo Receptors ◽  
Lateral Sclerosis

AbstractNogoA inhibits neurite outgrowth of motoneurons (NOM) through interaction with its receptors, Nogo66/NgR. Inhibition of Nogo receptors rescues NOM, but not to the extent exhibited by NogoA-knockout mice, suggesting the presence of other pathways. We found that NogoA-overexpressing muscle cells reduced phosphoglycerate kinase 1 (Pgk1) secretion, resulting in inhibiting NOM. Apart from its glycolytic role and independent of the Nogo66 pathway, extracellular Pgk1 stimulated NOM by triggering a reduction of p-Cofilin-S3, a growth cone collapse marker, through decreasing a novel Rac1-GTP/p-Pak1-T423/p-P38-T180/p-MK2-T334/p-Limk1-S323/p-Cofilin-S3 molecular pathway. Not only did supplementary Pgk1 enhance NOM in defective cells, but injection of Pgk1 rescued denervation in muscle-specific NogoA-overexpression of zebrafish and an Amyotrophic Lateral Sclerosis mouse model, SOD1-G93A. Thus, Pgk1 secreted from muscle is detrimental to motoneuron synapse growth and maintenance.

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