Targeted Expression of TruncatedGluedDisrupts Giant Fiber Synapse Formation inDrosophila

Abstract

Glued(1) (Gl(1)) mutants produce a truncated protein that acts as a poison subunit and disables the cytoplasmic retrograde motor dynein. Heterozygous mutants have axonal defects in the adult eye and the nervous system. Here we show that selective expression of the poison subunit in neurons of the giant fiber (GF) system disrupts synaptogenesis between the GF and one of its targets, the tergotrochanteral motorneuron (TTMn). Growth and pathfinding by the GF axon and the TTMn dendrite are normal, but the terminal of the GF axon fails to develop normally and becomes swollen with large vesicles. This is a presynaptic defect because expression of truncated Glued restricted to the GF results in the same defect. When tested electrophysiologically, the flies with abnormal axons show a weakened or absent GF-TTMn connection. In Glued(1) heterozygotes, GF-TTMn synapse formation appears morphologically normal, but adult flies show abnormal responses to repetitive stimuli. This physiological effect is also observed when tetanus toxin is expressed in the GFs. Because the GF-TTMn is thought to be a mixed electrochemical synapse, the results show that Glued has a role in assembling both the chemical and electrical components. We speculate that disrupting transport of a retrograde signal disrupts synapse formation and maturation.

Neurotoxic protein expression reveals connections between the circadian clock and mating behavior in Drosophila

“…Several tools exist to eliminate or inactivate Drosophila pacemaker neurons, including agents that cause cell death, e.g., the proapoptotic genes hid and reaper (8), or those that inactivate neuronal function, e.g., ectopically expressed modified K ϩ channels (9, 10), tetanus-toxin light-chain (11), and abnormal synaptic proteins (12). This second group typically inhibits synaptic transmission and, as a consequence, interneuronal communication, but the neurons are still alive.…”

Neuronal Phenotype in the Mature Nervous System Is Maintained by Persistent Retrograde Bone Morphogenetic Protein Signaling

“…The following fly strains were used: FMRFa-lacZ (WF3-T2) (Allan et al, 2003); apterous md544 [referred to as ap GAL4 here (Allan et al, 2003) (Allen et al, 1999)]; UAS-ANF-GFP [pre-pro-atrial natruietic factor fused to emerald green fluorescent protein (emGFP) (Rao et al, 2001)]. The X chromosome insertion (Rao et al, 2001) was hopped (DWA) to chromosome III using standard methods of P-element mobilization.…”

“…We tested this hypothesis using mutant Glued (Glued DN ) (Allen et al, 1999). Glued mutation has been linked to familial and sporadic amyotrophic lateral sclerosis (ALS) (Puls et al, 2003;Münch et al, 2004).…”

A cGMP-Dependent Protein Kinase Gene, foraging, Modifies Habituation-Like Response Decrement of the Giant Fiber Escape Circuit in Drosophila

“…The thoracic portion of the circuit (activated in both long-and short-latency responses) can give information about how mutations affect neural functioning within a network of identified neurons. The TTM branch has a single electrochemical neuronal synapse onto the TTM motoneuron (King and Wyman 1980;Allen et al 1999;Blagburn et al 1999), whereas the DLM branch includes two synapses, an apparent electrochemical synapse of the cervical giant fiber onto the peripherally synapsing interneuron (PSI) neuron (Blagburn et al 1999) and cholinergic synapses of the PSI onto the DLM motoneurons (Gorczyca and Hall 1984; Fig. 1).…”