Actin turnover is required to prevent axon retraction driven by endogenous actomyosin contractility.
J Cell Biol
; 158(7): 1219-28, 2002 Sep 30.
Article
in En
| MEDLINE
| ID: mdl-12356866
ABSTRACT
Growth cone motility and guidance depend on the dynamic reorganization of filamentous actin (F-actin). In the growth cone, F-actin undergoes turnover, which is the exchange of actin subunits from existing filaments. However, the function of F-actin turnover is not clear. We used jasplakinolide (jasp), a cell-permeable macrocyclic peptide that inhibits F-actin turnover, to study the role of F-actin turnover in axon extension. Treatment with jasp caused axon retraction, demonstrating that axon extension requires F-actin turnover. The retraction of axons in response to the inhibition of F-actin turnover was dependent on myosin activity and regulated by RhoA and myosin light chain kinase. Significantly, the endogenous myosin-based contractility was sufficient to cause axon retraction, because jasp did not alter myosin activity. Based on these observations, we asked whether guidance cues that cause axon retraction (ephrin-A2) inhibit F-actin turnover. Axon retraction in response to ephrin-A2 correlated with decreased F-actin turnover and required RhoA activity. These observations demonstrate that axon extension depends on an interaction between endogenous myosin-driven contractility and F-actin turnover, and that guidance cues that cause axon retraction inhibit F-actin turnover.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Peptides, Cyclic
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Axons
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Actin Cytoskeleton
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Actomyosin
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Actins
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Depsipeptides
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Microtubules
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Neurons
/
Antineoplastic Agents
Type of study:
Guideline
Limits:
Animals
Language:
En
Journal:
J Cell Biol
Year:
2002
Document type:
Article
Affiliation country:
Estados Unidos