Allele Dmel\cac^NT27

General Information
Symbol	Dmel\cac^NT27	Species	D. melanogaster
Name		FlyBase ID	FBal0155529
Feature type	allele	Associated gene	Dmel\cac

Map ( GBrowse )
Allele class
Mutagen	ethyl methanesulfonate
Recent Updates
Description	What does this section display? This section contains items that were added to this record for each release. It currently only tracks new links between this FlyBase report and other FlyBase data classes (e.g. genes, references, stocks) or controlled vocabulary terms (e.g. GO, anatomy terms). What does this section not display? This section does not currently display links that were removed or gene model changes.
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FB2013_03
FB2013_02
All updates	Click here to see a list of all updates to this record from FB2010_08 and on.
Nature of the Allele
Allele class
Mutagen	ethyl methanesulfonate (Rieckhof et al., 2003)
Mutations Mapped to the Genome

Type Location Additional Notes References point mutation X:11,862,892..11,862,892 evidence=experimental na_change=C11862892T pr_change=R876C\|cac-PG,R876C\|cac-PH,R876C\|cac-PI,R876C\|c ac-PJ,R876C\|cac-PC,R876C\|cac-PA,R876C\|cac-PD,R876C\|cac-PF, R876C\|cac-PB,R876C\|cac-PE reported_na_change=C2626T reported_pr_change=R876C (Rieckhof et al., 2003)
Associated Sequence Data
DDBJ / EMBL / GenBank	DNA sequence Protein sequence Name

UniProtKB/Swiss-Prot
UniProtKB/TrEMBL

Progenitor genotype
Nature of the lesion	Statement Reference Amino acid replacement: R876C. Nucleotide substitution: C2626T. (Rieckhof et al., 2003)
Cytology
Phenotypic Data
Phenotypic Class
	flightless (with cac^20-3) (Rieckhof et al., 2003) neuroanatomy defective (with cac^S) (Lee and Wu, 2010) neuroanatomy defective \| larval stage (Rieckhof et al., 2003) neuroanatomy defective \| larval stage (with cac^20-3) (Rieckhof et al., 2003) neurophysiology defective (Gu et al., 2009) neurophysiology defective (with cac^20-3) (Rieckhof et al., 2003) neurophysiology defective \| adult stage \| heat sensitive (Ryglewski et al., 2012) paralytic \| heat sensitive (Rieckhof et al., 2003, Wang et al., 2004) short lived (with cac^20-3) (Rieckhof et al., 2003) uncoordinated (with cac^20-3) (Rieckhof et al., 2003) viable \| reduced (with cac^20-3) (Rieckhof et al., 2003)
Phenotype Manifest In
	bouton \| larval stage (Rieckhof et al., 2003) bouton \| larval stage (with cac^20-3) (Rieckhof et al., 2003) indirect flight muscle motor neuron MN5 \| heat sensitive (Ryglewski et al., 2012) neuromuscular junction \| larval stage (Rieckhof et al., 2003) neuromuscular junction \| larval stage (with cac^20-3) (Rieckhof et al., 2003) NMJ bouton \| supernumerary (with cac^S) (Lee and Wu, 2010)
Detailed Description
	Statement Reference 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. (Ryglewski et al., 2012) cac[S]/cac[NT27] trans-heterozygotes exhibit an increase in type M satellites (small boutons). (Lee and Wu, 2010) cac[NT27] 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 cac[NT27] mutants compared with wild-type. Whole-cell calcium currents in typical cac[TS3] mutant pupal neurons have smaller slow-inactivating components compared to wild-type. Slow-inactivating current density is reduced by 75% in cac[TS3] 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 cac[NT27] mutant pupal neurons. However, the fast-inactivating PLTXII-resistant current is unaffected. Slow-inactivating PLTXII-sensitive currents are reduced by 57% in cac[NT27] antennal lobe projection neurons, compared with wild-type. The fast-inactivating, PLTXII-resistant calcium current density in cac[NT27] neurons is similar in magnitude to wild-type. mEPSC frequency is reduced by 73% in cac[NT27] compared to wild-type antennal lobe projection neurons. (Gu et al., 2009) cac[NT27] homozygous larvae show no increase in the number of boutons per-neuromuscular junction. (Dickman et al., 2008) cac^NT27 mutants paralyse within seconds of exposure to 38^o. (Wang et al., 2004) Mutant flies show a rapid onset of uncoordination, seizure-like activity and loss of motor control when placed at 38^oC. The flies require progressively longer times to recover when returned to room temperature with increased length of exposure to 38^oC. cac^20-3/cac^NT27 flies are flightless, have an uncoordinated gait and have a reduced viability and life span. cac^20-3/cac^NT27 third instar larvae show a dramatic defect in evoked neurotransmitter release at the neuromuscular junction compared to controls at 22^oC. 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 cac^20-3/cac^NT27 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). cac^20-3/cac^NT27 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. (Rieckhof et al., 2003)
External Data
Linkouts
Interactions
	Show the genetic interaction network for Enhancers & Suppressors
Phenotypic Class
Suppressor of
Statement Reference cac^S/cac^NT27 is a suppressor of neuroanatomy defective phenotype of sei² (Lee and Wu, 2010)
Phenotype Manifest In
Suppressor of
Statement Reference cac^S/cac^NT27 is a suppressor of neuromuscular junction phenotype of sei² (Lee and Wu, 2010) cac^S/cac^NT27 is a suppressor of NMJ bouton \| supernumerary phenotype of sei² (Lee and Wu, 2010)
Additional Comments
Genetic Interactions
Statement Reference A cac[S]/cac[NT27] background suppresses satellite frequency in sei[2] mutants. Double mutants display a drastic decrease in both type B and M satellites, along with an even more pronounced reduction in the number of mature boutons and terminal branches. (Lee and Wu, 2010)
Xenogenetic Interactions
Statement Reference
Complementation & Rescue Data
Comments
Stocks ( 0 )

Notes on Origin
Discoverer

Comments
	Allelic series (decreasing severity): cac^NT27 > cac^TS3 > cac^TS4 > cac^TS5. (Rieckhof et al., 2003)
External Crossreferences & Linkouts
Other Crossreferences

Linkouts

Synonyms & Secondary IDs ( 3 )
Reported As
Symbol Synonym	cac^NT27 (Wang et al., 2004, Dickman et al., 2008, Gu et al., 2009, Ryglewski et al., 2012, Lee and Wu, 2010) Dmca1A^NT27 (Rieckhof et al., 2003) NT27 (Gu et al., 2009)
Name Synonym
Secondary FlyBase IDs

References ( 7 )
Research paper	Ryglewski et al., 2012, J. Physiol. 590(4): 809--825 Cav2 channels mediate low and high voltage-activated calcium currents in Drosophila motoneurons. [FBrf0217496] Lee and Wu, 2010, J. Neurosci. 30(47): 15821--15833 Orchestration of stepwise synaptic growth by k+ and Ca2+ channels in Drosophila. [FBrf0212405] Gu et al., 2009, J. Neurophysiol. 101(1): 42--53 Cav2-type calcium channels encoded by cac regulate AP-independent neurotransmitter release at cholinergic synapses in adult Drosophila brain. [FBrf0206947] Dickman et al., 2008, J. Neurosci. 28(1): 31--38 Mutations in a drosophila alpha(2)delta voltage-gated calcium channel subunit reveal a crucial synaptic function. [FBrf0202120] Wang et al., 2004, J. Neurosci. 24(19): 4518--4529 A Drosophila temperature-sensitive seizure mutant in phosphoglycerate kinase disrupts ATP generation and alters synaptic function. [FBrf0174860] Rieckhof et al., 2003, J. Biol. Chem. 278(42): 41099--41108 Presynaptic N-type calcium channels regulate synaptic growth. [FBrf0174769]
Abstract	Hall and Xu, 2005, A. Dros. Res. Conf. 46: 730A Genetics & pharmacology of calcium channel currents in Drosophila larval muscle. [FBrf0182894]

Allele Dmel\cacNT27

Allele Dmel\cac^NT27