Human Disease Model Report: anesthesia, response and mechanisms, syntaxin-related

General Information

Name

anesthesia, response and mechanisms, syntaxin-related

FlyBase ID

FBhh0001378

Disease Ontology Term

Parent Disease

OMIM

Overview

In C. elegans, mutation in the unc-64 gene, which encodes a syntaxin, was found to exhibit diminished sensitivity to the anesthetics isoflurane and halothane. Syntaxins are nervous system-specific proteins implicated in the docking of synaptic vesicles with the presynaptic plasma membrane via a SNARE complex. Cele\unc-64 is ortholgous to the Drosophila gene syntaxin 1A (Syx1A). There are multiple related genes in human; the most closely related are STX1A and STX1B.

Using mutations of the Dmel\Syx1A gene, work in Drosophila has confirmed and expanded upon these findings. Resistance to isoflurane anesthesia can be produced by transiently expressing truncated Syx1A proteins in adults. Using the anesthetic propofol, results suggest this anthestic interferes with a step in SNARE complex formation, resulting in clusters of non-functional syntaxin1A on the plasma membrane.

This system has been used to compare sleep with anesthetic-induced response using isoflurane. It is postulated that in addition to first activating sleep pathways, anesthetics subsequently decrease the efficacy of neurotransmission. In addition to causing activation of inhibitory GABAa receptors postsynaptically, it has been postulated that general anesthetics also inhibit neurotransmitter release presynaptically. The role of syntaxin supports the presynaptic effects of the tested anesthetics.

See also the FlyBase chemical reports for isoflurane (FBch0000347), propofol (FBch0000881), ketamine (FBch0001074), sevoflurane (FBch0000349), etomidate (FBch0001073).

[updated Mar. 2024 by FlyBase; FBrf0222196]

Disease Summary Information

Disease Summary: anesthesia, response and mechanisms, syntaxin-related

OMIM report

Human gene(s) implicated

Symptoms and phenotype

Genetics

Cellular phenotype and pathology

Molecular information

STX1A encodes a member of the syntaxin superfamily. Syntaxins are nervous system-specific proteins implicated in the docking of synaptic vesicles with the presynaptic plasma membrane. The STX1A protein is part of the SNARE (Soluble NSF Attachment Receptor) complex composed of SNAP25, STX1A and VAMP2 which mediates the fusion of synaptic vesicles with the presynaptic plasma membrane. [Gene Cards, STX1A; 2021.07.14]

(FlyBase Curators, 2013-)

Activation of inhibitory GABAa receptors plays a central role in the action of many clinically relevant general anesthetics. In addition, there is growing evidence that anesthetics can act at a presynaptic locus to inhibit neurotransmitter release (Xie et al, 2012; pubmed:23136341).

(FlyBase Curators, 2013-)

External links

Gene2Function (human gene): STX1B
Gene2Function (human gene): STX1A
Gene Cards: STX1B
Gene Cards: STX1A
MedlinePlus (gene): STX1B
MedlinePlus (gene): STX1A
MARRVEL (human gene): STX1B
MARRVEL (human gene): STX1A
NCBI (Entrez) gene: STX1B; syntaxin 1B
NCBI (Entrez) gene: STX1A; syntaxin 1A

Disease synonyms

Related Diseases

Related human health report(s)

anesthesia, response and mechanisms

Ortholog Information

Human gene(s) in FlyBase

Human gene (HGNC)

Symbol / Name

STX1A; syntaxin 1A

D. melanogaster ortholog (based on DIOPT)

Dmel\Syx1A

(DIOPT, 2013-)

Comments on ortholog(s)

Many to one: 5 human genes to 1 Drosophila gene; multiple related genes in both species.

Human gene (HGNC)

Symbol / Name

STX1B; syntaxin 1B

D. melanogaster ortholog (based on DIOPT)

Dmel\Syx1A

(DIOPT, 2013-)

Comments on ortholog(s)

Many to one: 5 human genes to 1 Drosophila gene; multiple related genes in both species.

Other mammalian ortholog(s) used

D. melanogaster Gene Information (1)

Dmel\Syx1A

Gene Snapshot

Contributions welcome

Molecular function (GO)

Cellular component (GO)

Gene Groups / Pathways

QA-SNARE

Comments on ortholog(s)

High-scoring ortholog of human STX1A and STX1B; moderate-scoring ortholog of human STX2, STX3, STX4. Dmel\Syx1A shares 70% identity and 83% similarity with human STX1A and STX1B.

Orthologs and Alignments from DRSC

DIOPT - DRSC Integrative Ortholog Prediction Tool - Click the link below to search for orthologs in Humans

H. sapiens (Human)

Other Genes Used: Viral, Bacterial, Synthetic (0)

Summary of Physical Interactions (38 groups)

Syx1A

protein-protein

Interacting group

Assay

References

Syx1A - αSnap

anti bait coimmunoprecipitation, western blot, two hybrid, experimental knowledge based

(Guruharsha et al., 2011, Yu et al., 2011, Xu et al., 2002)

Syx1A - AttD

experimental knowledge based

(Guruharsha et al., 2011)

Syx1A - Bet1

experimental knowledge based

(Guruharsha et al., 2011)

Syx1A - comt

anti bait coimmunoprecipitation, western blot

(Yu et al., 2011)

Syx1A - cpx

anti tag coimmunoprecipitation, western blot

(Iyer et al., 2013)

Syx1A - γSnap1

experimental knowledge based

(Guruharsha et al., 2011)

Syx1A - γSnap2

experimental knowledge based

(Guruharsha et al., 2011)

Syx1A - Gos28

experimental knowledge based

(Guruharsha et al., 2011)

Syx1A - koko

experimental knowledge based

(Guruharsha et al., 2011)

Syx1A - Membrin

experimental knowledge based

(Guruharsha et al., 2011)

Syx1A - Nsf2

experimental knowledge based

(Guruharsha et al., 2011)

Syx1A - nSyb

anti bait coimmunoprecipitation, western blot, phenotype-based detection assay, inferred by author, experimental knowledge based, comigration in sds page

(Wang et al., 2014, Guruharsha et al., 2011, Yu et al., 2011, Wang and Chapman, 2010, Niemeyer and Schwarz, 2000)

Syx1A - Past1

experimental knowledge based

(Guruharsha et al., 2011)

Syx1A - pnut

anti tag coimmunoprecipitation, anti tag western blot

(Bae et al., 2007)

Syx1A - Rme-8

experimental knowledge based

(Guruharsha et al., 2011)

Syx1A - Rop

pull down, molecular weight estimation by staining

(Ortega et al., 2018)

Syx1A - Sec20

experimental knowledge based

(Guruharsha et al., 2011)

Syx1A - Sec22

experimental knowledge based

(Guruharsha et al., 2011)

Syx1A - Septin1

anti tag coimmunoprecipitation, anti tag western blot

(Bae et al., 2007)

Syx1A - Slh

experimental knowledge based

(Guruharsha et al., 2011)

Syx1A - Snap24

experimental knowledge based, comigration in sds page, western blot, anti tag coimmunoprecipitation, Identification by mass spectrometry

(Gordon et al., 2017, Guruharsha et al., 2011, Niemeyer and Schwarz, 2000)

Syx1A - Snap25

pull down, western blot, phenotype-based detection assay, inferred by author, comigration in sds page, anti bait coimmunoprecipitation, experimental knowledge based

(Wang et al., 2014, Guruharsha et al., 2011, Yu et al., 2011, Wang and Chapman, 2010, Niemeyer and Schwarz, 2000)

Syx1A - Snap29

anti bait coimmunoprecipitation, western blot, experimental knowledge based, peptide massfingerprinting, pull down

(Morelli et al., 2014, Xu et al., 2014, Guruharsha et al., 2011)

Syx1A - Syb

anti tag coimmunoprecipitation, Identification by mass spectrometry, comigration in sds page, western blot, experimental knowledge based

(Gordon et al., 2017, Guruharsha et al., 2011, Niemeyer and Schwarz, 2000)

Syx1A - Syt1

pull down, western blot, phenotype-based detection assay, inferred by author

(Wang and Chapman, 2010, Littleton et al., 2001)

Syx1A - Syt4

phenotype-based detection assay, inferred by author

(Wang and Chapman, 2010)

Syx1A - Syx5

experimental knowledge based

(Guruharsha et al., 2011)

Syx1A - Syx7

experimental knowledge based

(Guruharsha et al., 2011)

Syx1A - Syx8

experimental knowledge based

(Guruharsha et al., 2011)

Syx1A - Syx13

experimental knowledge based

(Guruharsha et al., 2011)

Syx1A - Syx16

experimental knowledge based

(Guruharsha et al., 2011)

Syx1A - Syx18

experimental knowledge based

(Guruharsha et al., 2011)

Syx1A - Use1

experimental knowledge based

(Guruharsha et al., 2011)

Syx1A - Vamp7

experimental knowledge based, anti tag coimmunoprecipitation, Identification by mass spectrometry

(Gordon et al., 2017, Guruharsha et al., 2011)

Syx1A - Vha100-1

anti bait coimmunoprecipitation, western blot, pull down, bio-layer interferometry

(Wang et al., 2014, Williamson et al., 2010)

Syx1A - Vti1a

experimental knowledge based

(Guruharsha et al., 2011)

Syx1A - Ykt6

anti tag coimmunoprecipitation, Identification by mass spectrometry, experimental knowledge based

(Gordon et al., 2017, Guruharsha et al., 2011)

RNA-protein

Interacting group

Assay

References

Syx1A - TBPH

anti tag coimmunoprecipitation, quantitative reverse transcription pcr

(Romano et al., 2020)

Alleles Reported to Model Human Disease (Disease Ontology) (4 alleles)

Syx1A

Models Based on Experimental Evidence ( 0 )

Allele

Disease

Evidence

References

Modifiers Based on Experimental Evidence ( 4 )

Allele

Disease

Interaction

References

Syx1A^Δ229

ameliorates Huntington's disease

modeled by Hsap\HTT^{128Q.1-336.UAS}

(Kaltenbach et al., 2007)

modeled by Hsap\HTT^128Q.FL.UAS

(Romero et al., 2008)

Syx1A⁰⁶⁷³⁷

ameliorates Huntington's disease

modeled by Hsap\HTT^{128Q.1-336.UAS}

(Kaltenbach et al., 2007)

Syx1A^EP3215

exacerbates Huntington's disease

modeled by Hsap\HTT^{128Q.1-336.UAS}

(Kaltenbach et al., 2007)

Syx1A^UAS.cBa

ameliorates amyotrophic lateral sclerosis

modeled by TBPH^Δ23

(Romano et al., 2014)

modeled by TBPH^GD6943

(Romano et al., 2014)

exacerbates neuronal ceroid lipofuscinosis 4

modeled by Hsap\DNAJC5^L116Δ.UAS

(Imler et al., 2019)

Alleles Representing Disease-Implicated Variants

Genetic Tools, Stocks and Reagents

Sources of Stocks

Contact lab of origin for a reagent not available from a public stock center.

Bloomington Stock Center Disease Page

Related mammalian, viral, bacterial, or synthetic transgenes

Allele

Transgene

Publicly Available Stocks

Selected Drosophila transgenes

Allele

Transgene

Publicly Available Stocks

Syx1A^UAS.cBa

P{UAS-Syx1A.B}

P{UAS-Syx1A.B}2, y¹ w^*

RNAi constructs available

Allele

Transgene

Publicly Available Stocks

Syx1A^GD564

P{GD564}

w¹¹¹⁸; P{GD564}v33112

Syx1A^JF01829

P{TRiP.JF01829}

y¹ v¹; P{TRiP.JF01829}attP2

Syx1A^NIG.5448R

P{NIG.5448R}

Selected Drosophila classical alleles

Allele

Allele class

Mutagen

Publicly Available Stocks

Syx1A⁰⁶⁷³⁷

P-element activity

ry⁵⁰⁶ P{PZ}Syx1A⁰⁶⁷³⁷ eIF4EHP⁰⁶⁷³⁷/TM3, ry^RK Sb¹ Ser¹

Syx1A^EP3215

P-element activity

Syx1A^L371

loss of function allele

P-element activity

Syx1A^Δ229

loss of function allele

Delta2-3 transposase

Syx1A^Δ229 ry⁵⁰⁶/TM3, ry^RK Sb¹ Ser¹

Syx1A¹

loss of function allele

ethyl methanesulfonate

References (8)

Report Sections

Open Close