Your browser version may not work well with NCBI's Web applications. More information here...
1: Curr Biol. 2008 Jun 3;18(11):808-13. Epub 2008 May 22.
Related Articles, Links
Click here to read Click here to read
CED-10/Rac1 mediates axon guidance by regulating the asymmetric distribution of MIG-10/lamellipodin.

Quinn CC, Pfeil DS, Wadsworth WG.

Department of Pathology, Robert Wood Johnson Medical School, Piscataway, New Jersey 08854-5653, USA. quinncc@umdnj.edu

Axon migrations are guided by extracellular cues that induce asymmetric outgrowth activity in the growth cone. Several intracellular signaling proteins have been implicated in the guidance response. However, how these proteins interact to generate asymmetric outgrowth activity is unknown. Here, we present evidence that in C. elegans, the CED-10/Rac1 GTPase binds to and causes asymmetric localization of MIG-10/lamellipodin, a protein that regulates actin polymerization and has outgrowth-promoting activity in neurons. Genetic analysis indicates that mig-10 and ced-10 function together to orient axon outgrowth. The RAPH domain of MIG-10 binds to activated CED-10/Rac1, and ced-10 function is required for the asymmetric MIG-10 localization that occurs in response to the UNC-6/netrin guidance cue. We also show that asymmetric localization of MIG-10 in growth cones is associated with asymmetric concentrations of f-actin and microtubules. These results suggest that CED-10/Rac1 is asymmetrically activated in response to the UNC-6/netrin signal and thereby causes asymmetric recruitment of MIG-10/lamellipodin. We propose that the interaction between activated CED-10/Rac1 and MIG-10/lamellipodin triggers local cytoskeletal assembly and polarizes outgrowth activity in response to UNC-6/netrin.

Publication Types:
PMID: 18499456 [PubMed - indexed for MEDLINE]