Related Experiment Video
Updated: Jun 25, 2026
Osmotic Avoidance in Caenorhabditis elegans: Synaptic Function of Two Genes, Orthologues of Human NRXN1 and NLGN1, as Candidates for Autism
Published on: December 11, 2009
C. elegans CARMIL negatively regulates UNC-73/Trio function during neuronal development
Pamela J Vanderzalm1, Amita Pandey, Michael E Hurwitz
1Molecular and Cell Biology, University of California, Berkeley, CA 94720, USA.
Abstract:
Whereas many molecules that promote cell and axonal growth cone migrations have been identified, few are known to inhibit these processes. In genetic screens designed to identify molecules that negatively regulate such migrations, we identified CRML-1, the C. elegans homolog of CARMIL. Although mammalian CARMIL acts to promote the migration of glioblastoma cells, we found that CRML-1 acts as a negative regulator of neuronal cell and axon growth cone migrations. Genetic evidence indicates that CRML-1 regulates these migrations by inhibiting the Rac GEF activity of UNC-73, a homolog of the Rac and Rho GEF Trio. The antagonistic effects of CRML-1 and UNC-73 can control the direction of growth cone migration by regulating the levels of the SAX-3 (a Robo homolog) guidance receptor. Consistent with the hypothesis that CRML-1 negatively regulates UNC-73 activity, these two proteins form a complex in vivo. Based on these observations, we propose a role for CRML-1 as a novel regulator of cell and axon migrations that acts through inhibition of Rac signaling.
Insights
CRML-1, a CARMIL homolog, inhibits neuronal cell and axon growth cone migrations by blocking Rac signaling. This finding reveals CRML-1 as a novel negative regulator of cell migration pathways.
Area of Science:
- Neuroscience
- Cell Biology
- Molecular Biology
Background:
- Limited knowledge exists regarding molecules that inhibit cell and axonal growth cone migrations.
- Mammalian CARMIL promotes glioblastoma cell migration, suggesting diverse roles for CARMIL family proteins.
Purpose of the Study:
- To identify novel inhibitors of neuronal cell and axon growth cone migrations.
- To elucidate the molecular mechanism by which CRML-1 regulates these processes in *C. elegans*.
Main Methods:
- Genetic screens in *C. elegans* to identify negative regulators of migration.
- Analysis of CRML-1's interaction with UNC-73, a Rac GEF.
- Investigation of CRML-1's role in regulating the SAX-3 (Robo homolog) guidance receptor.
Main Results:
- CRML-1 was identified as a negative regulator of neuronal cell and axon growth cone migrations in *C. elegans*.
- CRML-1 inhibits the Rac GEF activity of UNC-73, a Trio homolog.
- CRML-1 and UNC-73 form a complex in vivo, and their antagonism influences SAX-3 levels and growth cone guidance.
Conclusions:
- CRML-1 acts as a novel inhibitor of cell and axon migrations by antagonizing Rac signaling.
- The CRML-1/UNC-73 interaction provides a mechanism for regulating neuronal migration direction.
- CRML-1 represents a potential therapeutic target for conditions involving aberrant cell migration.
