Research the Nonet laboratory is focused on understanding how synapse development is orchestrated at the molecular level. The approach is based on combining molecular biology, cell biology, imaging, and genetics to define the role of genes in both orchestrating synapse formation during development and stabilizing them during adult life. The lab uses primarily the mechanosensory neurons of C. elegans as a model, but also perform some studies using zebrafish. Current projects in the lab include:
1) Coordinate regulation of a synaptogenesis transcription program. The lab has previously demonstrated that the transcriptional co-factor SSDP disrupts a portion of the synaptic development program in mechanosensory neurons resulting in synaptic branches with disorganized presynaptic varicosities that no longer co-localize active zone and synaptic vesicles. One component of this transcriptional program mediated through SSDP is repressing the transcription of the PIM-related kinase PRK-2. Our current work is aimed at defining other targets of SSDP as well as the targets of PRK-2 which are orchestrating presynaptic terminal maturation.
2) Characterization of the molecular mechanisms that initiate collateral branch outgrowth during synapse development. C. elegans PLM mechanosensory neurons form a single collateral branch on which the synapses of this neuron develop. In wild type animals, each PLM neuron forms one, and only one, branch at a precise point in development and at a stereotypic position on the anterior-posterior (A-P) axis. We’ve identified mutants that fail to form these branches, form too many branches, and form branches in ectopic positions on the A-P axis. The lab aims to understand the molecular mechanisms that initiate branching, limit branch formation to a single branch, and define the positioning of branching through molecular and cell biological characterization of these mutants.
3) Regulation of trafficking of synaptic vesicle precursors to synapses. The laboratory has identified components of the BORC complex (biogenesis of lysosomal organelle related complex) that disrupt trafficking of synaptic vesicle precursors from the soma to the synapse without disrupting trafficking of other synaptic components such as mitochondria and active zone proteins. In fibroblasts, the BORC complex regulates recruitment of kinesin molecular motors to lysosomes. In neurons, our studies have demonstrated that some components of the BORC complex also are involved in regulating trafficking of synaptic vesicle precursors. Current work is aimed at understanding how these proteins regulate movements of distinct organelles in the same cell.
- Nonet ML. Efficient transgenesis in caenorhabditis elegans using flp recombinase-mediated cassette exchange. Genetics. 2020; 215(4)903-921.
- Luo S, Schaefer AM, Dour S, Nonet ML. The conserved LIM domain-containing focal adhesion protein ZYX-1 regulates synaptic maintenance in Caenorhaditis elegans. Development. 2014; 141:3922-33.
- Zheng Q, Ahlawat S, Schaefer AM, Mahoney T, Koushika S, and Nonet ML. The vesicle protein SAM-4 regulates the processivity of synaptic vesicle transport. PLoS Genetics. 2014; 10: e1004644.
- Marcette J, Chen JJ, Nonet ML. The C. elegans microtubule minus end binding homolog PTRN-1 stabilizes synapses and neurites. eLife. 2014; 3:e01637.
- Mesa R, Luo S, Hoover CM, Miller K, Minniti A, Inestrosa N, Nonet ML. HID-1, a new component of the peptidergic signaling pathway. Genetics. 2011; 187:467-83.
- Zheng Q, Schaefer AM, Nonet ML. Regulation of C. elegans presynaptic differentiation and neurite branching via a novel signaling pathway initiated by SAM-10. Development. 2011; 138:87-96.
- Bounoutas A, Zheng Q, Nonet ML, Chalfie M. mec-15 encodes an F-box protein required for touch receptor neuron mechanosensation, synapse formation and development. Genetics. 2009; 183:607-17.
- Mahoney TR, Luo S, Round EK, Brauner M, Gottschalk A, Thomas JH, Nonet ML. Intestinal signaling to GABAergic neurons regulates a rhythmic behavior in Caenorhabditis elegans. PNAS. 2008; 105:16350-16355.
- Koushika S, Schaefer A, Vincent R, Willis JH, Bowerman B, Nonet ML. Mutations in C. elegans cytoplasmic dynein components reveal specificity of neuronal retrograde cargo. J Neurosci. 2004; 24:3907-17.
- Koushika S, Richmond JE, Hadwiger G, Weimer RM, Jorgensen EM, Nonet ML. A post-docking role for active zone protein Rim. Nat Neurosci. 2001; 4:997-1005.
- Schaefer AM, Hadwiger GD, Nonet ML. rpm-1, a conserved neuronal gene that regulates targeting and synaptogenesis in C. elegans. Neuron. 2000; 26: 345-56.
See a complete list of Dr. Nonet’s publications on PubMed.
1984, BS, University of California, Davis
1989, PhD, Massachusetts Institute of Technology
1995-1997 Searle Scholar
1995-1997 McKnight Scholar
1998 Molecular Biology of the Cell, Paper of the Year