scholarly journals Selective axonal translation of prenylated Cdc42 mRNA isoform supports axon growth

2018 ◽  
Author(s):  
Seung Joon Lee ◽  
Amar N. Kar ◽  
Matthew D. Zdradzinski ◽  
Priyanka Patel ◽  
Pabitra K. Sahoo ◽  
...  
Keyword(s):  
Axon Regeneration ◽  
Growth Promotion ◽  
Axon Growth ◽  
Alternatively Spliced ◽  
Selective Localization ◽  
Summary Statement ◽  
Growth Promoting ◽  
Axon Specification ◽  
Mrna Isoform

ABSTRACTThe small Rho-family GTPase Cdc42 has long been known to have a role in cell motility and axon growth. The eukaryotic CDC42 gene is alternatively spliced to generate mRNAs with two different 3’UTRs that encode proteins with distinct C-termini. The C-termini of these Cdc42 proteins include CAAX and CCAX motifs for post-translational prenylation and palmitoylation, respectively. Palmitoyl-Cdc42 protein was previously shown to contribute to dendrite maturation, while the prenyl-Cdc42 protein contributes to axon specification and its mRNA was detected in neurites. Here, we show that the mRNA encoding prenyl-Cdc42 isoform preferentially localizes into PNS axons and this localization selectively increases in vivo during PNS axon regeneration. Isoform specific siRNA knockdowns, rescue experiments with siRNA-resistant Cdc42 isoforms, and pharmacologically targeting Cdc42 activity indicate that prenyl-Cdc42 promotes axon growth while the palmitoyl-Cdc42 has little growth promoting activity. The growth promotion by prenyl-Cdc42 requires axonal mRNA localization with localized translation and an intact C-terminal CaaX motif for localized prenylation of the encoded protein. Together, these data show that alternative splicing of the CDC42 gene product generates an axon growth promoting locally synthesized prenyl-Cdc42 protein.SUMMARY STATEMENTAxon regeneration drives selective localization of alternatively spliced CDC42 isoform to PNS axons.

scholarly journals Selective axonal translation of the mRNA isoform encoding prenylated Cdc42 supports axon growth

2021 ◽  
Vol 134 (7) ◽  
Author(s):  
Seung Joon Lee ◽  
Matthew D. Zdradzinski ◽  
Pabitra K. Sahoo ◽  
Amar N. Kar ◽  
Priyanka Patel ◽  
...  
Keyword(s):  
Axon Growth ◽  
Functional Studies ◽  
Alternatively Spliced ◽  
Growth Promoting ◽  
Rho Family ◽  
Axon Specification ◽  
Axonal Targeting ◽  
Mrna Isoform ◽  
Caax Motif

ABSTRACT The small Rho-family GTPase Cdc42 has long been known to have a role in cell motility and axon growth. The eukaryotic Ccd42 gene is alternatively spliced to generate mRNAs with two different 3′ untranslated regions (UTRs) that encode proteins with distinct C-termini. The C-termini of these Cdc42 proteins include CaaX and CCaX motifs for post-translational prenylation and palmitoylation, respectively. Palmitoyl-Cdc42 protein was previously shown to contribute to dendrite maturation, while the prenyl-Cdc42 protein contributes to axon specification and its mRNA was detected in neurites. Here, we show that the mRNA encoding prenyl-Cdc42 isoform preferentially localizes into PNS axons and this localization selectively increases in vivo during peripheral nervous system (PNS) axon regeneration. Functional studies indicate that prenyl-Cdc42 increases axon length in a manner that requires axonal targeting of its mRNA, which, in turn, needs an intact C-terminal CaaX motif that can drive prenylation of the encoded protein. In contrast, palmitoyl-Cdc42 has no effect on axon growth but selectively increases dendrite length. Together, these data show that alternative splicing of the Cdc42 gene product generates an axon growth promoting, locally synthesized prenyl-Cdc42 protein. This article has an associated First Person interview with one of the co-first authors of the paper.

scholarly journals B-RAF kinase drives developmental axon growth and promotes axon regeneration in the injured mature CNS

2014 ◽  
Vol 211 (5) ◽  
pp. 801-814 ◽  
Author(s):  
Kevin J. O’Donovan ◽  
Kaijie Ma ◽  
Hengchang Guo ◽  
Chen Wang ◽  
Fang Sun ◽  
...  
Keyword(s):  
Optic Nerve ◽  
Axon Regeneration ◽  
Axon Growth ◽  
Loss Of Function ◽  
Pten Loss ◽  
Raf Kinase ◽  
Central Nervous Systems ◽  
Neurotrophin Signaling ◽  
Peripheral Sensory

Activation of intrinsic growth programs that promote developmental axon growth may also facilitate axon regeneration in injured adult neurons. Here, we demonstrate that conditional activation of B-RAF kinase alone in mouse embryonic neurons is sufficient to drive the growth of long-range peripheral sensory axon projections in vivo in the absence of upstream neurotrophin signaling. We further show that activated B-RAF signaling enables robust regenerative growth of sensory axons into the spinal cord after a dorsal root crush as well as substantial axon regrowth in the crush-lesioned optic nerve. Finally, the combination of B-RAF gain-of-function and PTEN loss-of-function promotes optic nerve axon extension beyond what would be predicted for a simple additive effect. We conclude that cell-intrinsic RAF signaling is a crucial pathway promoting developmental and regenerative axon growth in the peripheral and central nervous systems.

scholarly journals Akt1-Inhibitor of DNA binding2 is essential for growth cone formation and axon growth and promotes central nervous system axon regeneration

eLife ◽  
2016 ◽  
Vol 5 ◽  
Author(s):  
Hyo Rim Ko ◽  
Il-Sun Kwon ◽  
Inwoo Hwang ◽  
Eun-Ju Jin ◽  
Joo-Ho Shin ◽  
...  
Keyword(s):  
Growth Cone ◽  
Axonal Regeneration ◽  
Potential Role ◽  
Axon Regeneration ◽  
Hippocampal Slices ◽  
Axon Growth ◽  
Mechanistic Studies ◽  
Cone Formation ◽  
Growth Promoting ◽  
Inhibitor Of Dna Binding

Mechanistic studies of axon growth during development are beneficial to the search for neuron-intrinsic regulators of axon regeneration. Here, we discovered that, in the developing neuron from rat, Akt signaling regulates axon growth and growth cone formation through phosphorylation of serine 14 (S14) on Inhibitor of DNA binding 2 (Id2). This enhances Id2 protein stability by means of escape from proteasomal degradation, and steers its localization to the growth cone, where Id2 interacts with radixin that is critical for growth cone formation. Knockdown of Id2, or abrogation of Id2 phosphorylation at S14, greatly impairs axon growth and the architecture of growth cone. Intriguingly, reinstatement of Akt/Id2 signaling after injury in mouse hippocampal slices redeemed growth promoting ability, leading to obvious axon regeneration. Our results suggest that Akt/Id2 signaling is a key module for growth cone formation and axon growth, and its augmentation plays a potential role in CNS axonal regeneration.

scholarly journals Injury-free priming: induction of Primary Afferent Collateral Sprouting in uninjured sensory neurons in vivo primes them for enhanced axon outgrowth in vitro

2018 ◽  
Author(s):  
Sara Soleman ◽  
Jeffrey C. Petruska ◽  
Lawrence D.F. Moon
Keyword(s):  
Axon Regeneration ◽  
Axonal Injury ◽  
Axon Growth ◽  
Drg Neurons ◽  
Primary Afferent ◽  
Collateral Sprouting ◽  
Axon Elongation ◽  
Defined Media

AbstractPrior “conditioning” nerve lesions can prime DRG neurons for enhanced axon regeneration. Here, we tested the hypothesis that adult DRG neurons can be primed for axon elongation in vitro without axonal injury by prior induction of Primary Afferent Collateral Sprouting (PACS) in vivo. Thoracic cutaneous nerves (T9, T10, T12, T13 but not T11) were transected to create zones of denervated skin. Neurons from the uninjured T11 DRG underwent PACS within the skin, as demonstrated by the expansion of its zones responsive to pinch up to 14 days. At 7 or 14 days after induction of collateral sprouting, DRG neurons were dissociated and cultured for 18 hours in defined media lacking neurotrophins and growth factors. Neurons from the uninjured T11 DRG had longer mean neurite lengths than neurons from naïve DRG. A larger proportion of neurons from the uninjured T11 DRG showed an elongating or arborizing phenotype than neurons from naïve DRG. Transcriptomic analysis of the uninjured T11 DRG and denervated/reinnervated skin reveal regulation of receptor/ligand systems and regulators of growth during collateral sprouting. For example, the glial cell-derived neurotrophic family ligands Artemin and Persephin were upregulated in denervated skin after 7 and/or 14 days. We suggest that extracellular cues in denervated skin modify the intrinsic growth program of uninjured DRG neurons that enhances their ability to elongate or arborize even after explantation. Collectively, these data confirm that induction of collateral sprouting does not induce an injury response yet primes many of these uninjured neurons for in vitro axon growth.

scholarly journals Plant growth promoting endophyte Burkholderia contaminans NZ antagonizes phytopathogen Macrophomina phaseolina through melanin synthesis and pyrrolnitrin inhibition

PLoS ONE ◽  
2021 ◽  
Vol 16 (9) ◽  
pp. e0257863
Author(s):  
Nazia R. Zaman ◽  
Umar F. Chowdhury ◽  
Rifath N. Reza ◽  
Farhana T. Chowdhury ◽  
Mrinmoy Sarker ◽  
...  
Keyword(s):  
Plant Growth ◽  
Growth Promotion ◽  
Genome Mining ◽  
Gene Clusters ◽  
Macrophomina Phaseolina ◽  
Melanin Synthesis ◽  
Burkholderia Contaminans ◽  
Plant Growth Promoting ◽  
Growth Promoting

The endophytic bacterium Burkholderia contaminans NZ was isolated from jute, which is an important fiber-producing plant. This bacterium exhibits significant growth promotion activity in in vivo pot experiments, and like other plant growth-promoting (PGP) bacteria fixes nitrogen, produces indole acetic acid (IAA), siderophore, and 1-aminocyclopropane-1-carboxylate (ACC) deaminase activity. B. contaminans NZ is considered to exert a promising growth inhibitory effect on Macrophomina phaseolina, a phytopathogen responsible for infecting hundreds of crops worldwide. This study aimed to identify the possibility of B. contaminans NZ as a safe biocontrol agent and assess its effectiveness in suppressing phytopathogenic fungi, especially M. phaseolina. Co-culture of M. phaseolina with B. contaminans NZ on both solid and liquid media revealed appreciable growth suppression of M. phaseolina and its chromogenic aberration in liquid culture. Genome mining of B. contaminans NZ using NaPDoS and antiSMASH revealed gene clusters that displayed 100% similarity for cytotoxic and antifungal substances, such as pyrrolnitrin. GC-MS analysis of B. contaminans NZ culture extracts revealed various bioactive compounds, including catechol; 9,10-dihydro-12’-hydroxy-2’-methyl-5’-(phenylmethyl)- ergotaman 3’,6’,18-trione; 2,3-dihydro-3,5- dihydroxy-6-methyl-4H-pyran-4-one; 1-(1,6-Dioxooctadecyl)- pyrrolidine; 9-Octadecenamide; and 2- methoxy- phenol. These compounds reportedly exhibit tyrosinase inhibitory, antifungal, and antibiotic activities. Using a more targeted approach, an RP-HPLC purified fraction was analyzed by LC-MS, confirming the existence of pyrrolnitrin in the B. contaminans NZ extract. Secondary metabolites, such as catechol and ergotaman, have been predicted to inhibit melanin synthesis in M. phaseolina. Thus, B. contaminans NZ appears to inhibit phytopathogens by apparently impairing melanin synthesis and other potential biochemical pathways, exhibiting considerable fungistatic activity.

Homing behaviour of regenerating axons in the amphibian limb

Development ◽  
1989 ◽  
Vol 106 (4) ◽  
pp. 707-715
Author(s):  
S. Wilson ◽  
D.A. Tonge ◽  
N. Holder
Keyword(s):  
Electron Microscopy ◽  
Horseradish Peroxidase ◽  
Axon Regeneration ◽  
Axon Growth ◽  
Triturus Cristatus ◽  
Sequence Of Events ◽  
Growth Promoting ◽  
Directed Growth ◽  
Forearm Flexor ◽  
Over Time

Following peripheral nerve deviation in the limbs of urodele amphibians axons regrow distally toward their previous target muscles (Holder et al. 1984; Proc. Roy. Soc. Lond. B 222, 477–489). This study describes analysis of this axon regeneration over time following deviation of the forearm flexor nerve in Triturus cristatus and the extensor cranialis nerve in the axolotl. Using horseradish peroxidase (HRP) axonal tracing, electrophysiology and electron microscopy, we describe the sequence of events leading to reestablishment of functional innervation. HRP fills reveal axons leaving the deviated nerve via a number of possible routes and they invariably grow distally. Many axons take a path close to that of the original nerve but others fasciculate forming parallel paths. Electrophysiology and electron microscopy show that axons in the deviated region of the nerve degenerate extensively compared with cut, but undeviated, controls. The results are discussed in terms of the possible axon-growth-promoting mechanisms that result in directed growth.

Enhancement of verticillium wilt resistance in tomato transplants by in vitro co-culture of seedlings with a plant growth promoting rhizobacterium (Pseudomonas sp. strain PsJN)

1998 ◽  
Vol 44 (6) ◽  
pp. 528-536 ◽  
Author(s):  
V K Sharma ◽  
J Nowak
Keyword(s):  
Plant Growth ◽  
Verticillium Wilt ◽  
Plant Growth Promotion ◽  
Growth Promotion ◽  
Disease Suppression ◽  
Pseudomonas Sp ◽  
Plant Growth Promoting ◽  
Growth Promoting

The potential utilization of a plant growth promoting rhizobacterium, Pseudomonas sp. strain PsJN, to enhance the resistance of tomato transplants to verticillium wilt was investigated. Plant growth and disease development were tested on the disease-susceptible cultivar Bonny Best after Verticillium dahliae infection of tissue culture plantlets bacterized in vitro (by co-culturing with the bacterium) and seedlings bacterized in vivo (after 3 weeks growth in the greenhouse). Significant differences in both disease suppression and plant growth were obtained between in vitro bacterized and nonbacterized (control) plants. The degree of protection afforded by in vitro bacterization depended on the inoculum density of V. dahliae; the best and worst protection occurred at the lowest (103 conidia ·mL-1) and highest (106 conidia ·mL-1) levels, respectively. In contrast, the in vivo bacterized tomatoes did not show plant growth promotion when compared to the nonbacterized control plants. When challenged with Verticillium, significant growth differences between in vivo bacterized plants (26.8% for shoot height) and nonbacterized controls were only seen at the 3rd week after inoculation. Compared with the in vitro inoculation, there was no delay in the verticillium wilt symptom expression, even at the lowest concentration of V. dahliae, by in vivo PsJN inoculation. These results suggest that endophytic colonization of tomato tissues is required for the Verticillium-resistance responses. Plant growth promotion preceeds the disease-resistance responses and may depend on the colonization thresholds and subsequent sensitization of hosts.Key words: Pseudomonas sp., plant growth promoting rhizobacterium, Verticillium dahliae, tomato, colonization, plant growth promotion, disease suppression.

scholarly journals Overexpression of Reticulon 3 enhances CNS axon regeneration and functional recovery after injury

2021 ◽  
Author(s):  
Zubair Ahmed ◽  
Sharif Alhajlah ◽  
Adam Thompson
Keyword(s):  
Spinal Cord ◽  
Optic Nerve ◽  
Neurite Outgrowth ◽  
Functional Recovery ◽  
Axon Regeneration ◽  
Axon Growth ◽  
Dorsal Root Ganglion Neurons ◽  
Ganglion Neurons

CNS neurons are generally incapable of regenerating their axons after injury due to several intrinsic and extrinsic factors, including the presence of axon growth inhibitory molecules. One such potent inhibitor of CNS axon regeneration is Reticulon (RTN) 4 or Nogo-66. Here, we focused on RTN3 as its contribution in CNS axon regeneration is currently unknown. We found that RTN3 expression correlated with an axon regenerative phenotype in dorsal root ganglion neurons (DRGN) after injury to the dorsal columns, a model of spinal cord injury. Overexpression of RTN3 promoted disinhibited DRGN neurite outgrowth in vitro and dorsal column axon regeneration/sprouting and electrophysiological, sensory and locomotor functional recovery after injury in vivo. Knockdown of protrudin however, ablated RTN3-enhanced neurite outgrowth/axon regeneration in vitro and in vivo. Moreover, overexpression of RTN3 in a second model of CNS injury, the optic nerve crush injury model, enhanced retinal ganglion cell (RGC) survival, disinhibited neurite outgrowth in vitro and survival and axon regeneration in vivo, an effect that was also dependent on protrudin. These results demonstrate that RTN3 enhances neurite outgrowth/axon regeneration in a protrudin-dependent manner after both spinal cord and optic nerve injury.

scholarly journals Chronic neuronal activation increases dynamic microtubules to enhance functional axon regeneration after dorsal root crush injury

2020 ◽  
Vol 11 (1) ◽  
Author(s):  
Di Wu ◽  
Ying Jin ◽  
Tatiana M. Shapiro ◽  
Abhishek Hinduja ◽  
Peter W. Baas ◽  
...  
Keyword(s):  
Dorsal Root ◽  
Axon Regeneration ◽  
Axon Growth ◽  
Crush Injury ◽  
Neuronal Activation ◽  
Drg Neurons ◽  
Root Entry Zone ◽  
The Status

AbstractAfter a dorsal root crush injury, centrally-projecting sensory axons fail to regenerate across the dorsal root entry zone (DREZ) to extend into the spinal cord. We find that chemogenetic activation of adult dorsal root ganglion (DRG) neurons improves axon growth on an in vitro model of the inhibitory environment after injury. Moreover, repeated bouts of daily chemogenetic activation of adult DRG neurons for 12 weeks post-crush in vivo enhances axon regeneration across a chondroitinase-digested DREZ into spinal gray matter, where the regenerating axons form functional synapses and mediate behavioral recovery in a sensorimotor task. Neuronal activation-mediated axon extension is dependent upon changes in the status of tubulin post-translational modifications indicative of highly dynamic microtubules (as opposed to stable microtubules) within the distal axon, illuminating a novel mechanism underlying stimulation-mediated axon growth. We have identified an effective combinatory strategy to promote functionally-relevant axon regeneration of adult neurons into the CNS after injury.

Sign in / Sign up

Export Citation Format

Share Document