Allele Dmel\Syx1A^3-69

General Information
Symbol	Dmel\Syx1A^3-69	Species	D. melanogaster
Name		FlyBase ID	FBal0092503
Feature type	allele	Associated gene	Dmel\Syx1A
Also Known As	syx^3-69

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 (Littleton et al., 1998)
Mutations Mapped to the Genome

Type Location Additional Notes References point mutation 3R:19,929,405..19,929,405 evidence=experimental na_change=C19929405T pr_change=T254I\|Syx1A-PA reported_na_change=C?T reported_pr_change=T254I (Littleton et al., 1998)
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: T254I. (Lagow et al., 2007) Nucleotide substitution: C?T. (Lagow et al., 2007) Amino acid replacement: T254I. Nucleotide substitution: C?T. The T254I mutation lies in the 'a' position on the hydrophobic face of a heptad repeat at the end of the third coiled coil motif of the Syx1A protein, the H3 domain, three amino acids upstream of the C.botulinum C cleavage site. (Littleton et al., 1998)
Cytology
Phenotypic Data
Phenotypic Class
	neuroanatomy defective (Littleton et al., 1998) neurophysiology defective \| heat sensitive (Lagow et al., 2007) neurophysiology defective \| heat sensitive, with Scer\GAL4^elav-C155, Syx1A^Δ229, Syx1A^Scer\UAS.cBa (Lagow et al., 2007) neurophysiology defective \| heat sensitive (with Syx1A^Δ229) (Lagow et al., 2007) neurophysiology defective \| heat sensitive (with Syx1A^Δ229), with Scer\GAL4^elav-C155, Syx1A^Scer\UAS.cBa (Lagow et al., 2007) paralytic \| heat sensitive (Huang et al., 2006, Lagow et al., 2007) paralytic \| semidominant \| heat sensitive (Littleton et al., 1998) uncoordinated \| dominant \| heat sensitive (van Swinderen and Greenspan, 2005) visual behavior defective \| recessive \| heat sensitive (Littleton et al., 1998)
Phenotype Manifest In
	optic cartridge & synaptic vesicle (Littleton et al., 1998) retina (Littleton et al., 1998)
Detailed Description
	Statement Reference Syx1A[3-69] homozygous mutants show similar levels of synaptic vesicle endocytosis at the larval neuromuscular junction compared to control animals at both 25[o]C and 37[o]C. (Vijayakrishnan et al., 2009) Syx1A^3-69 mutant flies are rapidly paralysed at 38^oC but recover within 3 minutes when returned to a permissive temperature after a 20 minute period of paralysis. While Syx1A^3-69 mutant flies are paralysed at 38^oC, they are not motionless, they constantly shake their legs and abdomens. Repetitive and phase-locked leg shaking is easily observed in Syx1A^3-69 flies at both the permissive temperature (20^oC) and the restrictive temperature (38^oC) following artificial stimulus of the giant fiber neuron. The synaptic response of the dorsal longitudinal indirect flight muscles from Syx1A^3-69 flies is maintained at 38^oC. During observations, the intracellular electrodes are often dislodged from the dorsal longitudinal indirect flight muscles only from Syx1A^3-69 flies, along with a high incidence of spontaneous action potentials in the mutant muscles, indicating that synaptic transmission is not blocked at restrictive temperatures in Syx1A^3-69 flies. Light-induced 'on' and 'off' transient potentials of electroretinograms are not blocked by exposure of the Syx1A^3-69 fly to the restrictive temperature. In fact, the 'on' transient potential is slightly increased in amplitude at 38^oC. The average amount of 7S SNARE complex is significantly increased in Syx1A^3-69 mutants compared to wild-type, at 22^oC. Similarly, the level of SNARE multimers is also significantly increased in the mutant. The frequency of constitutive (or spontaneous) release of miniature excitatory postsynaptic potentials (mEPSPs) from third instar larval body-wall muscles innervated by motoneurons is dramatically increased some 7-fold in Syx1A^3-69 flies, compared to the wild-type. The average mini amplitude is similar in both the Syx1A^3-69 mutant and the wild-type larvae, suggesting that quanta and postsynaptic receptors likely remain normal. The unusually high rate of spontaneous release remains in the Syx1A^3-69 mutant in the absence of extracellualr Ca²⁺, although the resting potential is no different to wild-type. The mini frequency remains 13-fold higher in Syx1A^3-69 mutants compared to the wild-type in Ca²⁺-free saline containing the membrane-permeable Ca²⁺ chelator EGTA-AM. The amplitude of evoked EPSPs is significantly increased to 37mV in the Syx1A^3-69 mutant from 25mV in the wild-type. Because the average mini amplitude is not significantly different between the mutant and the wild-type, this increase in EPSP amplitude most likely reflects an enhancement in presynaptic release. There is a 2-fold increase in quantal content in the mutant compared to the wild-type. Syx1A^3-69 mutants do no exhibit a detectable difference in synaptic vesicle recycling compared to wild-type. The resting potential of the muscle fiber in Syx1A^3-69/+ and Syx1A^3-69/Syx1A^3-69 mutants is not significantly different from that in the wild-type. In Syx1A^3-69/+ mutants the frequency of spontaneous fusion is significantly higher than that in the wild-type, but much lower than that in the homozygote. The amplitude of evoked EPSPs in Syx1A^3-69/+ mutants is similar to that in homozygotes, but significantly higher than that in the wild-type. In Syx1A^3-69/Syx1A^Δ229 mutants, the mini-frequency is 22.3Hz, which is significantly higher than in the wild-type larvae. At 0.8mM Ca²⁺, the evoked EPSP amplitude is significantly increased to 37.9mV from 29.5mV in the wild-type larvae. These results are similar to those found in Syx1A^3-69 homozygotes. Neuronal expression of Syx1A^Scer\UAS.cBa under the control of Scer\GAL4^elav-C155 in Syx1A^3-69/Syx1A^Δ229 results in a dramatic reduction in the frequency of constitutive secretion to 8.8Hz from 24.9Hz. The average amplitude of EPSPs is also significantly reduced in Syx1A^3-69/Syx1A^Δ229 mutants expressing Syx1A^Scer\UAS.cBa under the control of Scer\GAL4^elav-C155. This EPSP amplitude is similar to that in Syx1A^Scer\UAS.cBa/Scer\GAL4^elav-C155 flies, but significantly higher than wild-type. (Lagow et al., 2007) After 10 minutes at 33^oC, Syx1A^3-69 homozygotes display only approximately 10% paralysis. Paralysed Syx1A^3-69 flies completely recover to an upright position within 1-2 minutes after returning to room temperature. (Huang et al., 2006) Heterozygous flies lose coordination as the temperature is raised, such that at 39^oC, they display a "bottom-dwelling" phenotype when placed in glass test tubes, in contrast to wild-type flies at this temperature, which are able to run up and down the sides of the tube for several minutes before also becoming uncoordinated. Homozygotes "pass out" completely in seconds at 39^oC. (van Swinderen and Greenspan, 2005) In ERG assay, mutants lose the on/off transients at 38^oC. Recovery of transients at 20^oC is rapid. Paralysis occurs after temperature shift to 38^oC. Kinetics of onset of paralysis are quicker for homozygotes than for heterozygotes. ERG phenotypes correlate with paralytic phenotypes: time course of paralysis and recovery for Syx1A mutants is more rapid than for comt mutants. Ultrastructural studies reveal that the number of synaptic vesicles in photoreceptor terminals in the optic cartridge is dramatically increased. Clear increases occur in the number of vesicles clustered round T-bars. Number of docked vesicles is increased compared to wild type. (Littleton et al., 1998)
External Data
Linkouts
Interactions
	Show the genetic interaction network for Enhancers & Suppressors
Phenotypic Class
Enhanced by
Statement Reference Syx1A^3-69 has paralytic \| heat sensitive phenotype, enhanceable by stmA[+]/stmA¹ (Huang et al., 2006) Syx1A^3-69 has paralytic \| heat sensitive phenotype, enhanceable by stmA¹ (Huang et al., 2006)
Suppressed by
Statement Reference Syx1A^3-69 has uncoordinated \| dominant \| heat sensitive phenotype, suppressible by Act42A[+]/Act42A^EP2096/Scer\GAL4[-] (van Swinderen and Greenspan, 2005) Syx1A^3-69 has uncoordinated \| dominant \| heat sensitive phenotype, suppressible by aop^EP598/aop[+]/Scer\GAL4[-] (van Swinderen and Greenspan, 2005) Syx1A^3-69 has uncoordinated \| dominant \| heat sensitive phenotype, suppressible by CG3760^EP548/CG3760[+]/Scer\GAL4[-] (van Swinderen and Greenspan, 2005) Syx1A^3-69 has uncoordinated \| dominant \| heat sensitive phenotype, suppressible by CG9894[+]/Bacc^EP7/Scer\GAL4[-] (van Swinderen and Greenspan, 2005) Syx1A^3-69 has uncoordinated \| dominant \| heat sensitive phenotype, suppressible by EP2[+]/EP2^EP2/Scer\GAL4[-] (van Swinderen and Greenspan, 2005) Syx1A^3-69 has uncoordinated \| dominant \| heat sensitive phenotype, suppressible by EP454[+]/EP454^EP454/Scer\GAL4[-] (van Swinderen and Greenspan, 2005) Syx1A^3-69 has uncoordinated \| dominant \| heat sensitive phenotype, suppressible by EP704^EP704/EP704[+]/Scer\GAL4[-] (van Swinderen and Greenspan, 2005) Syx1A^3-69 has uncoordinated \| dominant \| heat sensitive phenotype, suppressible by EP718[+]/EP718^EP718/Scer\GAL4[-] (van Swinderen and Greenspan, 2005) Syx1A^3-69 has uncoordinated \| dominant \| heat sensitive phenotype, suppressible by EP1244^EP1244/Scer\GAL4[-]/EP1244[+] (van Swinderen and Greenspan, 2005) Syx1A^3-69 has uncoordinated \| dominant \| heat sensitive phenotype, suppressible by Etl1^EP701/CG5899[+]/Scer\GAL4[-] (van Swinderen and Greenspan, 2005) Syx1A^3-69 has uncoordinated \| dominant \| heat sensitive phenotype, suppressible by Gmd^EP315/Scer\GAL4[-]/Gmd[+] (van Swinderen and Greenspan, 2005) Syx1A^3-69 has uncoordinated \| dominant \| heat sensitive phenotype, suppressible by kis^EP563/kis[+]/Scer\GAL4[-] (van Swinderen and Greenspan, 2005) Syx1A^3-69 has uncoordinated \| dominant \| heat sensitive phenotype, suppressible by MESR4[+]/Scer\GAL4[-]/MESR4^EP386 (van Swinderen and Greenspan, 2005) Syx1A^3-69 has uncoordinated \| dominant \| heat sensitive phenotype, suppressible by Pdk[+]/Pdk^EP547/Scer\GAL4[-] (van Swinderen and Greenspan, 2005) Syx1A^3-69 has uncoordinated \| dominant \| heat sensitive phenotype, suppressible by RpS23[+]/RpS23^EP638/Scer\GAL4[-] (van Swinderen and Greenspan, 2005) Syx1A^3-69 has uncoordinated \| dominant \| heat sensitive phenotype, suppressible by Scer\GAL4[-]/EP364[+]/EP364^EP364 (van Swinderen and Greenspan, 2005)
Enhancer of
Statement Reference Syx1A^3-69 is an enhancer of paralytic \| heat sensitive phenotype of stmA¹ (Huang et al., 2006)
Phenotype Manifest In
Other
Statement Reference Syx1A^3-69, stmA¹ has garland cell \| wandering third instar larval stage \| temperature conditional phenotype (Vijayakrishnan et al., 2009) Syx1A^3-69, stmA¹ has NMJ bouton \| larval stage \| temperature conditional phenotype (Vijayakrishnan et al., 2009)
Additional Comments
Genetic Interactions
Statement Reference stmA[1]; Syx1A[3-69] double mutants show a strong reduction in synaptic vesicle endocytosis at the larval neuromuscular junction compared to control animals at both 25[o]C and 37[o]C. stmA[1]; Syx1A[3-69] double mutants show endocytosis activity in garland cells at 25[o]C. At 37[o]C no endocytosis is observed. (Vijayakrishnan et al., 2009) stmA¹; Syx1A^3-69 double mutants rapidly paralyse at 33^oC, with approximately 90% of mutants completely paralysed within 10 minutes. Approximately 5 minutes are required for all paralysed stmA¹; Syx1A^3-69 double mutants to regain an upright position after return to room temperature. stmA¹/stmA¹; Syx1A^3-69/Syx1A^3-69 homozygotes and stmA¹/stmA^rev499; Syx1A^3-69/Syx1A^3-69 double mutants exhibit an indistinguishable synergistic genetic interaction. (Huang et al., 2006)
Xenogenetic Interactions
Statement Reference
Complementation & Rescue Data
Fails to complement	Syx1A^Δ229 (Littleton et al., 1998)
Rescued by	Syx1A^3-69 is rescued by Syx1A^+t13 (Littleton et al., 1998)
Partially rescued by	Syx1A^3-69 is partially rescued by Scer\GAL4^elav-C155/Syx1A^Δ229/Syx1A^Scer\UAS.cBa/Syx1A^Scer\UAS.cBa (Lagow et al., 2007)
Partially rescues	Scer\GAL4^elav-C155, Syx1A^3-69, Syx1A^Scer\UAS.cBa, Syx1A^Scer\UAS.cBa partially rescues Syx1A^Δ229 (Lagow et al., 2007)
Comments
Stocks ( 0 )

Notes on Origin
Discoverer

External Crossreferences & Linkouts
Other Crossreferences

Linkouts

Synonyms & Secondary IDs ( 5 )
Reported As
Symbol Synonym	syx1A^3-69 Syx1A^3-69 syx^3-69 (Montana and Littleton, 2001, Littleton et al., 1998, Lagow et al., 2007, Huang et al., 2006, Barber et al., 2009, Vijayakrishnan et al., 2009) ts^3-69 (Littleton et al., 1998)
Name Synonym	syntaxin^3-69 (Vijayakrishnan et al., 2009)
Secondary FlyBase IDs

References ( 7 )
Research paper	Barber et al., 2009, J. Cell Biol. 187(2): 295--310 Postsynaptic regulation of synaptic plasticity by synaptotagmin 4 requires both C2 domains. [FBrf0208997] Vijayakrishnan et al., 2009, J. Cell Sci. 122(1): 114--125 Rolling blackout is required for bulk endocytosis in non-neuronal cells and neuronal synapses. [FBrf0206896] Lagow et al., 2007, PLoS Biol. 5(4): e72 Modification of a hydrophobic layer by a point mutation in syntaxin 1A regulates the rate of synaptic vesicle fusion. [FBrf0201324] Huang et al., 2006, J. Neurosci. 26(9): 2369--2379 Rolling blackout is required for synaptic vesicle exocytosis. [FBrf0191047] van Swinderen and Greenspan, 2005, Genetics 169(4): 2151--2163 Flexibility in a gene network affecting a simple behavior in Drosophila melanogaster. [FBrf0188513] Littleton et al., 1998, Neuron 21(2): 401--413 Temperature-sensitive paralytic mutations demonstrate that synaptic exocytosis requires SNARE complex assembly and disassembly. [FBrf0104474]
Abstract	Montana and Littleton, 2001, Bellen, Taylor, 2001: 37 Genetic and molecular identification of novel syntaxin interacting proteins. [FBrf0144616]

Allele Dmel\Syx1A3-69

Allele Dmel\Syx1A^3-69