Amino acid replacement: S483L.
Single missense mutation due to at GC to AT transition.
C13260925T
S483L | comt-PA; S483L | comt-PB
S483L
Site of nucleotide substitution in mutant inferred by FlyBase based on reported amino acid change.
comt1/comt1 mutants exhibit severely reduced lifespans when reared at 29[o]C, a milder reduced lifespan phenotype when reared at 22[o]C; display normal climbing ability when reared at 22[o]C, but progressive loss of climbing ability after shifting to 29[o]C; loss of dopaminergic neurons in the PPL1 cluster after 48h at 29[o]C; decreased survival during prolonged starvation during adulthood at 22[o]C; normal initiation but defective maintenance of starvation-induced autophagy in the larval fat body, with fewer and larger lysosomes and loss of autophagic flux after 12 hours of starvation; loss of autophagic activity in a subset of PPL1 dopaminergic neurons after adults are placed at 29[o]C for 36 hrs, and impaired lysosome trafficking in the brain after adults are placed at 29[o]C for 48 hrs, as compared with wild type flies.
Duration of copulation in mutant males is significantly shorter than in wild-type males. Mutant flies show a severe locomotor impairment. Mutant flies take longer to recover from mechanical shock than normal.
Electroretinograms taken from the retina at 38oC reveal losses of on/off transients in mutants.
The action potentials of the dorsal longitudinal flight muscle (DLM) are indistinguishable from wild-type at the permissive temperature. At the restrictive temperature an activity-dependent reduction in the DLM action potential and postsynaptic potential is seen. The number of docked vesicles per active zone is higher than wild-type in the neuromuscular synapses of the coxal muscles (at the restrictive temperature).
In ERG assay, mutants lose the on/off transients at 38oC, though over a slower time course than for Syx1A3-69. Recovery of transients at 20oC is slower than for Syx1A3-69. ERG phenotypes correlate with paralytic phenotypes: time course of paralysis and recovery for Syx1A mutants is more rapid than for comt mutants.
Paralysis normally occurs within 1-2 minutes of exposure to 38oC. comt1 flies bearing P{hsp70-NSF} exposed to heat shock, followed by one day recovery, are highly resistant to exposure to 38oC.
comt1 has short lived phenotype, non-suppressible by sei2/sei2
comt1 has abnormal locomotor behavior | adult stage | progressive | heat sensitive phenotype, non-suppressible by sei2/sei2
comt1 has abnormal neuroanatomy | adult stage | heat sensitive phenotype, non-suppressible by sei2/sei2
comt1 has dopaminergic PPL1 neuron | heat sensitive phenotype, non-suppressible by sei2/sei2
ovr1 accelerates the paralysis observed in comt1 animals at 36oC (the time for 50% paralysis is reduced). At 36oC, cacTS2 comt1 double mutants show faster paralysis than comt1 single mutants at this temperature. At 38oC, cacTS2 comt1 double mutants show faster rapid paralysis than in cacTS2 single mutants at this temperature.
Siddiqi and Benzer.