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Originally published as Genetics Published Articles Ahead of Print on August 3, 2009.

Genetics, Vol. 183, 607-617, October 2009, Copyright © 2009
doi:10.1534/genetics.109.105726

mec-15 Encodes an F-Box Protein Required for Touch Receptor Neuron Mechanosensation, Synapse Formation and Development

Alexander Bounoutas*, Qun Zheng{dagger}, Michael L. Nonet{dagger} and Martin Chalfie*,1

* Department of Biological Sciences, Columbia University, New York, New York 10027 and {dagger} Department of Anatomy and Neurobiology, Washington University School of Medicine, St. Louis, Missouri 63110

1 Corresponding author: Department of Biological Sciences, 1012 Fairchild Bldg., MC#2446, Columbia University, 1212 Amsterdam Ave., New York, NY 10027.
E-mail: mc21{at}columbia.edu

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 β-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.