Amino acid replacement: R876C. Nucleotide substitution: C2626T.
C11968859T
C2626T
R876C | cac-PA; R876C | cac-PB; R876C | cac-PC; R876C | cac-PD; R876C | cac-PE; R876C | cac-PF; R876C | cac-PG; R876C | cac-PH; R876C | cac-PI; R876C | cac-PJ; R876C | cac-PL; R876C | cac-PM; R982C | cac-PN; R876C | cac-PO; R876C | cac-PP; R876C | cac-PS; R876C | cac-PT; R876C | cac-PU
R876C
flightless (with cac20-3)
short lived (with cac20-3)
bouton | larval stage (with cac20-3)
NMJ bouton | increased number (with cacS)
cacNT27 mutants exhibit a dramatic reduction in air puff-triggered flight initiation success. However, these flies display spontaneous sustained flight, with significantly increased wing beat frequency coupled with higher DLM firing rates well beyond the maximum firing frequency found in wild-type flies.
Mutant adults raised at a permissive temperature of 20[o]C and then shifted to a restrictive temperature of 32[0]C prior to electrophysiological analysis show alterations in the calcium currents of the MN5 neuron. On average, the maximal low voltage activated current amplitude is reduced by 64 +/- 9% and sustained high voltage amplitude current amplitude is close to zero.
cacNT27 homozygous mutant flies appear less active than wild-type flies, even at room temperature.
Using a negative geotaxis assay, the mean distance climbed is reduced by 51% in cacNT27 mutants compared with wild-type.
Whole-cell calcium currents in typical cacTS3 mutant pupal neurons have smaller slow-inactivating components compared to wild-type. Slow-inactivating current density is reduced by 75% in cacTS3 mutants compared with wild-type neurons. This decrease in density is not due to a shift in voltage dependence because the current-density-voltage curves and the normalised conductance-voltage curves are similar.
Addition of PLTXII (Plectreurys toxin II) does not further reduce the slow-inactivating current density found in cacNT27 mutant pupal neurons. However, the fast-inactivating PLTXII-resistant current is unaffected.
Slow-inactivating PLTXII-sensitive currents are reduced by 57% in cacNT27 antennal lobe projection neurons, compared with wild-type. The fast-inactivating, PLTXII-resistant calcium current density in cacNT27 neurons is similar in magnitude to wild-type.
mEPSC frequency is reduced by 73% in cacNT27 compared to wild-type antennal lobe projection neurons.
cacNT27 homozygous larvae show no increase in the number of boutons per-neuromuscular junction.
cacNT27 mutants paralyse within seconds of exposure to 38o.
Mutant flies show a rapid onset of uncoordination, seizure-like activity and loss of motor control when placed at 38oC. The flies require progressively longer times to recover when returned to room temperature with increased length of exposure to 38oC. cac20-3/cacNT27 flies are flightless, have an uncoordinated gait and have a reduced viability and life span. cac20-3/cacNT27 third instar larvae show a dramatic defect in evoked neurotransmitter release at the neuromuscular junction compared to controls at 22oC. At low extracellular calcium levels, evoked release is undetectable in the mutant larvae, whereas control larvae show substantial synaptic transmission. At higher extracellular calcium levels, evoked release is partially restored in the mutant larvae, but the quantal content is greatly reduced compared to controls. The amplitude of the miniature excitatory junctional potential is unchanged in the mutant larvae compared to controls. Homozygous and cac20-3/cacNT27 third instar larvae show a significant reduction in the number of varicosities at the neuromuscular junction of muscle fibres 6 and 7 compared to wild-type larvae (varicosity number per muscle surface area is also reduced). cac20-3/cacNT27 third instar larvae also show a significant reduction in the number of varicosities at the neuromuscular junction of muscle fibre 4. Homozygous larvae show reduced axonal terminal branching at the neuromuscular junction and a smaller synaptic innervation domain. Homozygous embryos show no defect in the number of varicosities or innervation pattern at the neuromuscular junction of muscle fibres 6 and 7.
cacS/cacNT27 is a suppressor of abnormal neuroanatomy phenotype of sei2
cacS/cacNT27 is a suppressor of NMJ bouton | increased number phenotype of sei2
cacS/cacNT27 is a suppressor of neuromuscular junction phenotype of sei2
Allelic series (decreasing severity): cacNT27 > cacTS3 > cacTS4 > cacTS5.