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Published on: August 18, 2008
A Farnesyltransferase Acts to Inhibit Ectopic Neurite Formation in C. elegans
David Carr1,2, Leticia Sanchez-Alvarez1,2, Janice H Imai1
1Neuroscience Program, Ottawa Hospital Research Institute, Ottawa, Ontario, Canada.
Abstract:
Genetic pathways that regulate nascent neurite formation play a critical role in neuronal morphogenesis. The core planar cell polarity components VANG-1/Van Gogh and PRKL-1/Prickle are involved in blocking inappropriate neurite formation in a subset of motor neurons in C. elegans. A genetic screen for mutants that display supernumerary neurites was performed to identify additional factors involved in this process. This screen identified mutations in fntb-1, the β subunit of farnesyltransferase. We show that fntb-1 is expressed in neurons and acts cell-autonomously to regulate neurite formation. Prickle proteins are known to be post-translationally modified by farnesylation at their C-terminal CAAX motifs. We show that PRKL-1 can be recruited to the plasma membrane in both a CAAX-dependent and CAAX-independent manner but that PRKL-1 can only inhibit neurite formation in a CAAX-dependent manner.
Insights
Farnesyltransferase subunit beta (fntb-1) regulates neurite formation in C. elegans neurons. This protein is crucial for proper neuronal development by enabling Prickle protein function.
Area of Science:
- Neuroscience
- Developmental Biology
- Genetics
Background:
- Neurite formation is essential for neuronal development and is regulated by complex genetic pathways.
- Planar cell polarity proteins, such as VANG-1/Van Gogh and PRKL-1/Prickle, are known to control neurite outgrowth in specific neurons.
- Understanding the molecular mechanisms governing neurite development is key to comprehending neuronal morphogenesis.
Purpose of the Study:
- To identify novel genetic factors involved in regulating nascent neurite formation.
- To elucidate the role of farnesyltransferase subunit beta (fntb-1) in neuronal development.
- To investigate the mechanism by which PRKL-1/Prickle regulates neurite formation, specifically its dependence on post-translational modification.
Main Methods:
- A forward genetic screen was employed in C. elegans to isolate mutants with supernumerary neurites.
- Mutations in fntb-1 were identified and characterized.
- Expression patterns of fntb-1 in neurons were analyzed.
- Cell-autonomous functions of fntb-1 in neurite formation were assessed.
- The role of farnesylation and the CAAX motif in PRKL-1/Prickle localization and function was investigated.
Main Results:
- Mutations in fntb-1, encoding the beta subunit of farnesyltransferase, were found to cause defects in neurite formation.
- fntb-1 is expressed in neurons and functions cell-autonomously to regulate neurite outgrowth.
- While PRKL-1/Prickle can localize to the plasma membrane through both CAAX-dependent and independent mechanisms, its inhibitory function on neurite formation requires CAAX-dependent farnesylation.
Conclusions:
- fntb-1 is a novel and essential regulator of neurite formation in C. elegans.
- The farnesylation of PRKL-1/Prickle, mediated by fntb-1, is critical for its role in preventing inappropriate neurite outgrowth.
- These findings highlight the importance of post-translational modification in the function of planar cell polarity proteins during neuronal development.
