A Farnesyltransferase Acts to Inhibit Ectopic Neurite Formation in C. elegans.
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.
Neuroscience Program, Ottawa Hospital Research Institute, Ottawa, Ontario, Canada.|Department of Cellular and Molecular Medicine, University of Ottawa, Ottawa, Ontario, Canada.
David
D
Carr
Neuroscience Program, Ottawa Hospital Research Institute, Ottawa, Ontario, Canada.|Department of Cellular and Molecular Medicine, University of Ottawa, Ottawa, Ontario, Canada.
Leticia
L
Sanchez-Alvarez
Neuroscience Program, Ottawa Hospital Research Institute, Ottawa, Ontario, Canada.
Janice H
JH
Imai
Neuroscience Program, Ottawa Hospital Research Institute, Ottawa, Ontario, Canada.
Cristina
C
Slatculescu
Neuroscience Program, Ottawa Hospital Research Institute, Ottawa, Ontario, Canada.|Department of Cellular and Molecular Medicine, University of Ottawa, Ottawa, Ontario, Canada.
Nathaniel
N
Noblett
Department of Biochemistry, Duke University Medical Center, Durham, North Carolina, United States of America.
Lei
L
Mao
Department of Biochemistry, Duke University Medical Center, Durham, North Carolina, United States of America.
Lorena
L
Beese
Neuroscience Program, Ottawa Hospital Research Institute, Ottawa, Ontario, Canada.|Department of Cellular and Molecular Medicine, University of Ottawa, Ottawa, Ontario, Canada.|University of Ottawa Brain and Mind Research Institute, Ottawa, Ontario, Canada.
Antonio
A
Colavita
D000818:Animals; D017173:Caenorhabditis elegans / Q000502:physiology*; D029742:Caenorhabditis elegans Proteins / Q000032:analysis / Q000235:genetics / Q000378:metabolism*; D051231:Farnesyltranstransferase / Q000032:analysis / Q000235:genetics / Q000378:metabolism*; D047908:Intracellular Signaling Peptides and Proteins / Q000032:analysis / Q000235:genetics / Q000378:metabolism*; D008958:Models, Molecular; D009154:Mutation; D016501:Neurites / Q000502:physiology*; D054876:Prenylation; D011499:Protein Processing, Post-Translational; D021122:Protein Subunits / Q000032:analysis / Q000235:genetics / Q000378:metabolism
D029742:Caenorhabditis elegans Proteins; D047908:Intracellular Signaling Peptides and Proteins; C569184:PRKL-1 protein, C elegans; D021122:Protein Subunits; D051231:Farnesyltranstransferase