scholarly journals Slit holds a strange attraction for filopodia

2016 ◽  
Vol 213 (2) ◽  
pp. 138-138
Author(s):  
Ben Short
Keyword(s):  
Growth Cone ◽  
Guidance Cue ◽  
Strange Attraction

The guidance cue Slit induces axonal repulsion by directing the extension of growth cone filopodia.

scholarly journals Dynamic Microtubule Ends Are Required for Growth Cone Turning to Avoid an Inhibitory Guidance Cue

1997 ◽  
Vol 17 (9) ◽  
pp. 3085-3095 ◽  
Author(s):  
Jean F. Challacombe ◽  
Diane M. Snow ◽  
Paul C. Letourneau
Keyword(s):  
Growth Cone ◽  
Guidance Cue ◽  
Dynamic Microtubule

scholarly journals A pair of E3 ubiquitin ligases compete to regulate filopodial dynamics and axon guidance

2019 ◽  
Vol 219 (1) ◽  
Author(s):  
Nicholas P. Boyer ◽  
Laura E. McCormick ◽  
Shalini Menon ◽  
Fabio L. Urbina ◽  
Stephanie L. Gupton
Keyword(s):  
Axon Guidance ◽  
Growth Cone ◽  
Ubiquitin Ligases ◽  
Critical Element ◽  
E3 Ubiquitin Ligases ◽  
Related Protein ◽  
Guidance Cues ◽  
Guidance Cue ◽  
Neuronal Connections ◽  
Novel Model

Appropriate axon guidance is necessary to form accurate neuronal connections. Axon guidance cues that stimulate cytoskeletal reorganization within the growth cone direct axon navigation. Filopodia at the growth cone periphery have long been considered sensors for axon guidance cues, yet how they respond to extracellular cues remains ill defined. Our previous work found that the filopodial actin polymerase VASP and consequently filopodial stability are negatively regulated via nondegradative TRIM9-dependent ubiquitination. Appropriate VASP ubiquitination and deubiquitination are required for axon turning in response to the guidance cue netrin-1. Here we show that the TRIM9-related protein TRIM67 outcompetes TRIM9 for interacting with VASP and antagonizes TRIM9-dependent VASP ubiquitination. The surprising antagonistic roles of two closely related E3 ubiquitin ligases are required for netrin-1–dependent filopodial responses, axon turning and branching, and fiber tract formation. We suggest a novel model in which coordinated regulation of VASP ubiquitination by a pair of interfering ligases is a critical element of VASP dynamics, filopodial stability, and axon guidance.

scholarly journals RHO-1 and the Rho GEF RHGF-1 interact with UNC-6/Netrin signaling to regulate growth cone protrusion and microtubule organization in C. elegans

2019 ◽  
Author(s):  
Mahekta R. Gujar ◽  
Aubrie M. Stricker ◽  
Erik A. Lundquist
Keyword(s):  
Axon Guidance ◽  
Growth Cone ◽  
Neural Circuit ◽  
Growth Cones ◽  
Negative Regulator ◽  
Microtubule Organization ◽  
C Elegans ◽  
Guidance Cue ◽  
Rho Gef

AbstractUNC-6/Netrin is a conserved axon guidance cue that directs growth cone migrations in the dorsal-ventral axis of C. elegans and in the vertebrate spinal cord. UNC-6/Netrin is expressed in ventral cells, and growth cones migrate ventrally toward or dorsally away from UNC-6/Netrin. Recent studies of growth cone behavior during outgrowth in vivo in C. elegans have led to a polarity/protrusion model in directed growth cone migration away from UNC-6/Netrin. In this model, UNC-6/Netrin first polarizes the growth cone via the UNC-5 receptor, leading to dorsally biased protrusion and F-actin accumulation. UNC-6/Netrin then regulates protrusion based on this polarity. The receptor UNC-40/DCC drives protrusion dorsally, away from the UNC-6/Netrin source, and the UNC-5 receptor inhibits protrusion ventrally, near the UNC-6/Netrin source, resulting in dorsal migration. UNC-5 inhibits protrusion in part by excluding microtubules from the growth cone, which are pro-protrusive. Here we report that the RHO-1/RhoA GTPase and its activator GEF RHGF-1 inhibit growth cone protrusion and MT accumulation in growth cones, similar to UNC-5. However, growth cone polarity of protrusion and F-actin were unaffected by RHO-1 and RHGF-1. Thus, RHO-1 signaling acts specifically as a negative regulator of protrusion and MT accumulation, and not polarity. Genetic interactions suggest that RHO-1 and RHGF-1 act with UNC-5, as well as with a parallel pathway, to regulate protrusion. The cytoskeletal interacting molecule UNC-33/CRMP was required for RHO-1 activity to inhibit MT accumulation, suggesting that UNC-33/CRMP might act downstream of RHO-1. In sum, these studies describe a new role of RHO-1 and RHGF-1 in regulation of growth cone protrusion by UNC-6/Netrin.Author SummaryNeural circuits are formed by precise connections between axons. During axon formation, the growth cone leads the axon to its proper target in a process called axon guidance. Growth cone outgrowth involves asymmetric protrusion driven by extracellular cues that stimulate and inhibit protrusion. How guidance cues regulate growth cone protrusion in neural circuit formation is incompletely understood. This work shows that the signaling molecule RHO-1 acts downstream of the UNC-6/Netrin guidance cue to inhibit growth cone protrusion in part by excluding microtubules from the growth cone, which are structural elements that drive protrusion.

scholarly journals Nestin in immature embryonic neurons affects axon growth cone morphology and Semaphorin3a sensitivity

2019 ◽  
Vol 30 (10) ◽  
pp. 1214-1229 ◽  
Author(s):  
C. J. Bott ◽  
C. G. Johnson ◽  
C. C. Yap ◽  
N. D. Dwyer ◽  
K. A. Litwa ◽  
...  
Keyword(s):  
Growth Cone ◽  
Intermediate Filament ◽  
Cortical Neurons ◽  
Axon Growth ◽  
Neural Progenitors ◽  
Spatial Modulation ◽  
Nestin Expression ◽  
Guidance Cue ◽  
Newborn Neurons

Correct wiring in the neocortex requires that responses to an individual guidance cue vary among neurons in the same location, and within the same neuron over time. Nestin is an atypical intermediate filament expressed strongly in neural progenitors and is thus used widely as a progenitor marker. Here we show a subpopulation of embryonic cortical neurons that transiently express nestin in their axons. Nestin expression is thus not restricted to neural progenitors, but persists for 2–3 d at lower levels in newborn neurons. We found that nestin-expressing neurons have smaller growth cones, suggesting that nestin affects cytoskeletal dynamics. Nestin, unlike other intermediate filament subtypes, regulates cdk5 kinase by binding the cdk5 activator p35. Cdk5 activity is induced by the repulsive guidance cue Semaphorin3a (Sema3a), leading to axonal growth cone collapse in vitro. Therefore, we tested whether nestin-expressing neurons showed altered responses to Sema3a. We find that nestin-expressing newborn neurons are more sensitive to Sema3a in a roscovitine-sensitive manner, whereas nestin knockdown results in lowered sensitivity to Sema3a. We propose that nestin functions in immature neurons to modulate cdk5 downstream of the Sema3a response. Thus, the transient expression of nestin could allow temporal and/or spatial modulation of a neuron’s response to Sema3a, particularly during early axon guidance.

scholarly journals Anesthetics disrupt growth cone guidance cue sensing through actions on the GABAA α2 receptor mediated by the immature chloride gradient

2019 ◽  
Vol 74 ◽  
pp. 106812
Author(s):  
Jing Xu ◽  
Michael Xu ◽  
YuChia Wang ◽  
R. Paige Mathena ◽  
Jieqiong Wen ◽  
...  
Keyword(s):  
Growth Cone ◽  
Guidance Cue ◽  
Growth Cone Guidance

scholarly journals Nestin in immature embryonic neurons regulates axon growth cone morphology and Semaphorin3a sensitivity

2017 ◽  
Author(s):  
C.J. Bott ◽  
C. G. Johnson ◽  
C.C. Yap ◽  
N.D. Dwyer ◽  
K.A. Litwa ◽  
...  
Keyword(s):  
Growth Cone ◽  
Intermediate Filament ◽  
Cortical Neurons ◽  
Axon Growth ◽  
Neural Progenitors ◽  
Nestin Expression ◽  
Guidance Cue ◽  
Cytoskeletal Dynamics ◽  
Newborn Neurons

AbstractCorrect wiring in the neocortex requires that responses to an individual guidance cue vary among neurons in the same location, and within the same neuron over time. Nestin is an atypical intermediate filament expressed highly in neural progenitors and is thus used widely as a progenitor marker. Here we show a subpopulation of embryonic cortical neurons which transiently express nestin in their axons. Nestin expression is thus not restricted to neural progenitors but persists at lower levels in some newborn neurons for 2-3 days. We found that nestin-expressing neurons have smaller growth cones, suggesting that nestin affects cytoskeletal dynamics. Nestin, unlike other intermediate filament subtypes, regulates cdk5 kinase. Cdk5 activity is induced by the repulsive guidance cue Sema3a leading to growth cone collapse in vitro. Therefore, we tested whether nestin-expressing neurons showed altered responses to Sema3a. We find that nestin-expressing newborn neurons are more sensitive to Sema3a in a roscovitine-sensitive manner, whereas nestin knockdown results in lowered sensitivity to Sema3a. We propose that nestin functions in immature neurons to modulate cdk5 and thereby the Sema3a response. Thus, the transient expression of nestin could allow for temporal modulation of a neuron's response to Sema3a particularly during early axon guidance decisions.

scholarly journals The PH/MyTH4/FERMmolecule MAX-1 inhibits UNC-5 activity in regulation of VD growth cone protrusion in Caenorhabditis elegans

2021 ◽  
Author(s):  
Snehal S. Mahadik ◽  
Erik A. Lundquist
Keyword(s):  
Spinal Cord ◽  
Plasma Membrane ◽  
Axon Guidance ◽  
Growth Cone ◽  
Growth Cones ◽  
Genetic Interactions ◽  
Wild Type ◽  
C Elegans ◽  
Guidance Cue ◽  
Mechanistic Insight

UNC-6/Netrin is a secreted conserved guidance cue that regulates dorsal-ventral axon guidance of C. elegans and in the vertebral spinal cord. In the polarity/protrusion model of VD growth cone guidance away from ventrally-expressed UNC-6 (repulsion), UNC-6 first polarizes the growth cone via the UNC-5 receptor such that filopodial protrusions are biased dorsally. UNC-6 then regulates a balance of protrusion in the growth cone based upon this polarity. UNC-5 inhibits protrusion ventrally, and the UNC-6 receptor UNC-40/DCC stimulates protrusion dorsally, resulting in net dorsal growth cone outgrowth. UNC-5 inhibits protrusion through the flavin monooxygenases FMO-1, 4, and 5 and possible actin destabilization, and inhibits pro-protrusive microtubule entry into the growth cone utilizing UNC-33/CRMP. The PH/MyTH4/FERM myosin-like protein was previously shown to act with UNC-5 in VD axon guidance utilizing axon guidance endpoint analysis. Here, we analyzed the effects of MAX-1 on VD growth cone morphology during outgrowth. We found that max-1 mutant growth cones were smaller and less protrusive than wild-type, the opposite of the unc-5 mutant phenotype. Furthermore, genetic interactions suggest that MAX-1 might normally inhibit UNC-5 activity, such that in a max-1 mutant growth cone, UNC-5 is overactive. Our results, combined with previous studies suggesting that MAX-1 might regulate UNC-5 levels in the cell or plasma membrane localization, suggest that MAX-1 attenuates UNC-5 signaling by regulating UNC-5 stability or trafficking. In summary, in the context of growth cone protrusion, MAX-1 inhibits UNC-5, demonstrating the mechanistic insight that can be gained by analyzing growth cones during outgrowth in addition to axon guidance endpoint analysis.

scholarly journals A pair of E3 ubiquitin ligases compete to regulate filopodial dynamics and axon guidance TRIM67 regulates filopodial stability and axon guidance

2019 ◽  
Author(s):  
Nicholas P. Boyer ◽  
Laura E. McCormick ◽  
Fabio L. Urbina ◽  
Stephanie L. Gupton
Keyword(s):  
Axon Guidance ◽  
Growth Cone ◽  
Ubiquitin Ligases ◽  
Critical Element ◽  
Related Protein ◽  
Fiber Tract ◽  
Guidance Cues ◽  
Guidance Cue ◽  
Neuronal Connections ◽  
Novel Model

ABSTRACTAppropriate axon guidance is necessary to form accurate neuronal connections. Guidance cues stimulate reorganization of the cytoskeleton within the distal growth cone at the tip of the extending axon. Filopodia at the periphery of the growth cone have long been considered sensors for axon guidance cues, yet how they perceive and respond to extracellular cues remains ill-defined. Our previous work found that the filopodial actin polymerase VASP is regulated via TRIM9-dependent nondegradative ubiquitination, and that appropriate VASP ubiquitination and deubiquitination are required for axon turning in response to the guidance cue netrin-1. Here we show that the TRIM9-related protein TRIM67 antagonizes VASP ubiquitination by outcompeting the TRIM9:VASP interaction. This antagonistic role is required for netrin-1 dependent filopodial responses, axon turning and branching, and fiber tract formation. We suggest a novel model that coordinated regulation of nondegradative VASP ubiquitination by a pair of ligases is a critical element of axon guidance.

scholarly journals CRYP-2/cPTPRO is a neurite inhibitory repulsive guidance cue for retinal neurons in vitro

2001 ◽  
Vol 154 (4) ◽  
pp. 867-878 ◽  
Author(s):  
Laurie Stepanek ◽  
Qi Lun Sun ◽  
Jun Wang ◽  
Cong Wang ◽  
John L. Bixby
Keyword(s):  
Growth Cone ◽  
Protein Tyrosine Phosphatases ◽  
Axon Growth ◽  
Extracellular Domain ◽  
Receptor Protein ◽  
Projection Neurons ◽  
Retinal Neurons ◽  
Type Iii ◽  
Guidance Cue

Receptor protein tyrosine phosphatases (RPTPs) are implicated as regulators of axon growth and guidance. Genetic deletions in the fly have shown that type III RPTPs are important in axon pathfinding, but nothing is known about their function on a cellular level. Previous experiments in our lab have identified a type III RPTP, CRYP-2/cPTPRO, specifically expressed during the period of axon outgrowth in the chick brain; cPTPRO is expressed in the axons and growth cones of retinal and tectal projection neurons. We constructed a fusion protein containing the extracellular domain of cPTPRO fused to the Fc portion of mouse immunoglobulin G-1, and used it to perform in vitro functional assays. We found that the extracellular domain of cPTPRO is an antiadhesive, neurite inhibitory molecule for retinal neurons. In addition, cPTPRO had potent growth cone collapsing activity in vitro, and locally applied gradients of cPTPRO repelled growing retinal axons. This chemorepulsive effect could be regulated by the level of cGMP in the growth cone. Immunohistochemical examination of the retina indicated that cPTPRO has at least one heterophilic binding partner in the retina. Taken together, our results indicate that cPTPRO may act as a guidance cue for retinal ganglion cells during vertebrate development.

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