The dynein motor complex mediates retrograde transport of various cargos. However, relatively little is known about how the dynein motor complex is modulated and what its requirements are for cargo specificity. Previous reports have shown that synaptic proteins accumulate at the mechanosensory axonal termini of dynein mutants (Koushika et al, 2004). We identified several members of the dynein motor complex (light chain
dlc-1, light intermediate chain
dli-1 and predicted intermediate chain C17H12.1) in an RNAi screen for hypersensitivity to aldicarb (Hic), suggesting that loss of dynein function results in increased excitatory neurotransmission. We have since determined that loss of function mutations in additional dynein subunits (heavy chain
dhc-1, and dynactin
dnc-1) are also Hic. Preliminary results indicate that late endosome markers accumulate in the neurons of dynein mutants. This change in endosome morphology could reflect defects in retrograde transport of endocytic cargo. Because dynein defects produced a Hic phenotype, we suggest that other Hic or aldicarb resistant (Ric) mutants may have defects in dynein localization or function. To test this idea we are examining Hic and Ric mutants for changes in distribution of dynein subunits or of early and late endosomal markers. Understanding the regulation of the dynein motor complex appears to be a vital component of understanding negative regulation of synaptic transmission.