Regulation of neurotransmitter vesicles by the homeodomain protein UNC-4 and its transcriptional corepressor UNC-37/groucho in Caenorhabditis elegans cholinergic motor neurons

Kim M. Lickteig, Janet S. Duerr, Dennis L. Frisby, David H. Hall, James B. Rand, David M. Miller

Research output: Contribution to journalArticle

50 Citations (Scopus)

Abstract

Motor neuron function depends on neurotransmitter release from synaptic vesicles (SVs). Here we show that the UNC-4 homeoprotein and its transcriptional corepressor protein UNC-37 regulate SV protein levels in specific Caenorhabditis elegans motor neurons. UNC-4 is expressed in four classes (DA, VA, VC, and SAB) of cholinergic motor neurons. Antibody staining reveals that five different vesicular proteins (UNC-17, choline acetyltransferase, Synaptotagmin, Synaptobrevin, and RAB-3) are substantially reduced in unc-4 and unc-37 mutants in these cells; nonvesicular neuronal proteins (Syntaxin, UNC-18, and UNC-11) are not affected, however. Ultrastructural analysis of VA motor neurons in the mutant unc-4(e120) confirms that SV number in the presynaptic zone is reduced (∼40%) whereas axonal diameter and synaptic morphology are not visibly altered. Because the UNC-4-UNC-37 complex has been shown to mediate transcriptional repression, we propose that these effects are performed via an intermediate gene. Our results are consistent with a model in which this unc-4 target gene ("gene-x") functions at a post-transcriptional level as a negative regulator of SV biogenesis or stability. Experiments with a temperature-sensitive unc-4 mutant show that the adult level of SV proteins strictly depends on unc-4 function during a critical period of motor neuron differentiation, unc-4 activity during this sensitive larval stage is also required for the creation of proper synaptic inputs to VA motor neurons. The temporal correlation of these events may mean that a common unc-4-dependent mechanism controls both the specificity of synaptic inputs as well as the strength of synaptic outputs for these motor neurons.

Original languageEnglish (US)
Pages (from-to)2001-2014
Number of pages14
JournalJournal of Neuroscience
Volume21
Issue number6
StatePublished - Mar 15 2001

Fingerprint

Homeodomain Proteins
Co-Repressor Proteins
Cholinergic Neurons
Caenorhabditis elegans
Motor Neurons
Neurotransmitter Agents
Synaptic Vesicles
Vesicle-Associated Membrane Protein 3
Synaptotagmins
Qa-SNARE Proteins
Genes
Proteins
Choline O-Acetyltransferase
Staining and Labeling
Temperature
Antibodies

Keywords

  • C. elegans
  • Cholinergic differentiation
  • Neural development
  • Synaptic specificity
  • Synaptic vesicles
  • Unc-4

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Regulation of neurotransmitter vesicles by the homeodomain protein UNC-4 and its transcriptional corepressor UNC-37/groucho in Caenorhabditis elegans cholinergic motor neurons. / Lickteig, Kim M.; Duerr, Janet S.; Frisby, Dennis L.; Hall, David H.; Rand, James B.; Miller, David M.

In: Journal of Neuroscience, Vol. 21, No. 6, 15.03.2001, p. 2001-2014.

Research output: Contribution to journalArticle

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