mec-15 encodes an F-box protein required for touch receptor neuron mechanosensation, synapse formation and development.
Selective protein degradation is a key regulator of neuronal development and synaptogenesis. Complexes that target proteins for degradation often contain F-box proteins. Here we characterize MEC-15, an F-box protein with WD repeats, which is required for the development and function of Caenorhabditis elegans touch receptor neurons (TRNs). Mutations in mec-15 produce defects in TRN touch sensitivity, chemical synapse formation, and cell-body morphology. All mec-15 mutant phenotypes are enhanced by mutations in a MAP kinase pathway composed of the MAPKKK DLK-1, the MAPKK MKK-4, and the p38 MAPK PMK-3. A mutation of the rpm-1 gene, which encodes an E3 ubiquitin ligase that negatively regulates this pathway to promote synaptogenesis, suppresses only the mec-15 cell-body defect. Thus, MEC-15 acts in parallel with RPM-1, implicating a second protein degradation pathway in TRN development. In addition, all mec-15 phenotypes can be dominantly suppressed by mutations in mec-7, which encodes a beta-tubulin, and dominantly enhanced by mutations in mec-12, which encodes an alpha-tubulin. Since mec-15 phenotypes depend on the relative levels of these tubulins, MEC-15 may target proteins whose function is affected by these levels.
Bounoutas
Alexander
A
Department of Biological Sciences, Columbia University, New York, NY 10027, USA.
Zheng
Qun
Q
Nonet
Michael L
ML
Chalfie
Martin
M
D029742:Caenorhabditis elegans Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D044783:F-Box Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D005786:Gene Expression Regulation; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D008465:Mechanoreceptors / Q000166:cytology / Q000378:metabolism / Q000502:physiology*; D040542:Mechanotransduction, Cellular / Q000235:genetics / Q000502:physiology; D008856:Microscopy, Fluorescence; D009154:Mutation; D009474:Neurons / Q000166:cytology / Q000378:metabolism / Q000502:physiology*; D010641:Phenotype; D013569:Synapses / Q000502:physiology; D014110:Touch / Q000502:physiology*; D014404:Tubulin / Q000235:genetics / Q000378:metabolism; D048051:p38 Mitogen-Activated Protein Kinases / Q000235:genetics / Q000378:metabolism
D029742:Caenorhabditis elegans Proteins; D044783:F-Box Proteins; C115872:Mec-7 protein, C elegans; D014404:Tubulin; D049452:Green Fluorescent Proteins; D048051:p38 Mitogen-Activated Protein Kinases