unc-4 and
unc-37 are required for proper differentiation of specific motor neurons. The UNC-4 homeodomain protein is expressed in DA, VA, VC, and SAB motor neurons ("
unc-4 motor neurons").
unc-37 encodes a groucho-like corepressor protein that is ubiquitously expressed (1). In
unc-4 (
e120) and
unc-37 (
e262) mutants, VA motor neurons receive synaptic inputs normally reserved for their VB sister cells. To explain this effect, we have proposed that UNC-4 and UNC-37 function together to repress genes that normally specify a VB pattern of synaptic inputs.We have now shown that
unc-4 and
unc-37 activities are also required for the expression of normal levels of synaptic vesicle proteins in "
unc-4 motor neurons".
unc-17 encodes the vesicular acetylcholine transporter (VAChT) and
cha-1 encodes choline acetyltransferase (ChAT). Both of these proteins are associated with synaptic vesicles and are required for cholinergic function. The
unc-17 and
cha-1 genes are coordinately transcribed from a common promoter. In
unc-4 and
unc-37 mutants, antibody staining of UNC-17 and ChAT is substantially reduced in "
unc-4 motor neurons". However,
unc-4 and
unc-37 mutations do not decrease expression of a GFP reporter gene driven by the
unc-17-
cha-1 promoter. Since the levels of UNC-17 and ChAT proteins are decreased in
unc-4 and
unc-37 mutants whereas
unc-17-
cha-1 transcription is not affected, we hypothesize that
unc-4 and
unc-37 are regulating
unc-17 and
cha-1 via a post-transcriptional mechanism.
unc-4 and
unc-37 are also required for maintaining normal levels of synaptotagmin, an integral synaptic vesicle protein. The concomitant effects of
unc-4 and
unc-37 mutations on synaptotagmin, UNC-17 and ChAT may mean that
unc-4 and
unc-37 regulate expression of gene products involved in targeting proteins to synaptic vesicles or in general aspects of vesicle synthesis, trafficking, and/or stability. For example,
unc-4 and
unc-37 might repress a gene product that destabilizes vesicle proteins in "
unc-4 motor neurons." In this scenario, the activity of this hypothetical gene would be de-repressed in
unc-4 and
unc-37 mutants leading to high rates of vesicle turnover. A major goal of this work is to define the molecular mechanism of
unc-4 and
unc-37 action on synaptic vesicle protein expression. 1. Pflugrad, A., et al. (1997) Development 124, 1699-1709.