VTI1A Protein (Vesicle Transport Through Interaction with TIA-1 1A)

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VTI1A Protein (Vesicle Transport Through Interaction with TIA-1 1A)

Overview

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VTI1A Protein (Vesicle Transport Through Interaction with TIA-1 1A)

Overview

<table class="infobox infobox-protein">
<tr>
<th class="infobox-header" colspan="2">VTI1A Protein (Vesicle Transport Through Interaction with TIA-1 1A)</th>
</tr>
<tr>
<td class="label">Protein Name</td>
<td>Vesicle Transport through Interaction with TIA-1 1A</td>
</tr>
<tr>
<td class="label">Gene Symbol</td>
<td>VTI1A</td>
</tr>
<tr>
<td class="label">Alternative Names</td>
<td>TIA-1, TIA1-related protein, Vesicle transport protein</td>
</tr>
<tr>
<td class="label">Chromosomal Location</td>
<td>10q26.3</td>
</tr>
<tr>
<td class="label">UniProt ID</td>
<td>Q9NY26</td>
</tr>
<tr>
<td class="label">Entrez Gene ID</td>
<td>27153</td>
</tr>
<tr>
<td class="label">Protein Length</td>
<td>258 amino acids</td>
</tr>
<tr>
<td class="label">Molecular Weight</td>
<td>~29 kDa</td>
</tr>
<tr>
<td class="label">Protein Family</td>
<td>SNARE family, Qc-SNARE subclass</td>
</tr>
<tr>
<td class="label">Component</td>
<td>Type</td>
</tr>
<tr>
<td class="label">Synaptobrevin/VAMP</td>
<td>R-SNARE</td>
</tr>
<tr>
<td class="label">Syntaxin</td>
<td>Qa-SNARE</td>
</tr>
<tr>
<td class="label">SNAP-25</td>
<td>Qb + Qc-SNARE</td>
</tr>
<tr>
<td class="label">VTI1A</td>
<td>Qc-SNARE</td>
</tr>
<tr>
<td class="label">Region</td>
<td>Amino Acids</td>
</tr>
<tr>
<td class="label">N-terminal domain</td>
<td>1-80</td>
</tr>
<tr>
<td class="label">SNARE motif</td>
<td>81-220</td>
</tr>
<tr>
<td class="label">Transmembrane domain</td>
<td>221-258</td>
</tr>
<tr>
<td class="label">Function</td>
<td>Mechanism</td>
</tr>
<tr>
<td class="label">Vesicle priming</td>
<td>Assists in SNARE complex formation</td>
</tr>
<tr>
<td class="label">Fusion</td>
<td>Facilitates membrane merger</td>
</tr>
<tr>
<td class="label">Kinetics</td>
<td>Modulates release probability</td>
</tr>
<tr>
<td class="label">Short-term plasticity</td>
<td>Affects facilitation/depression</td>
</tr>
<tr>
<td class="label">Pathway</td>
<td>Vesicle Type</td>
</tr>
<tr>
<td class="label">Exocytosis</td>
<td>Secretory vesicles</td>
</tr>
<tr>
<td class="label">Endolysosomal</td>
<td>Late endosomes</td>
</tr>
<tr>
<td class="label">Autophagy</td>
<td>Autophagosomes</td>
</tr>
<tr>
<td class="label">Golgi trafficking</td>
<td>Golgi vesicles</td>
</tr>
<tr>
<td class="label">Tissue</td>
<td>Expression Level</td>
</tr>
<tr>
<td class="label">Brain</td>
<td>High</td>
</tr>
<tr>
<td class="label">Endocrine</td>
<td>High</td>
</tr>
<tr>
<td class="label">Kidney</td>
<td>Moderate</td>
</tr>
<tr>
<td class="label">Liver</td>
<td>Moderate</td>
</tr>
<tr>
<td class="label">Pancreas</td>
<td>Moderate</td>
</tr>
<tr>
<td class="label">Finding</td>
<td>Evidence</td>
</tr>
<tr>
<td class="label">Causative variants</td>
<td>Pathogenic mutations identified</td>
</tr>
<tr>
<td class="label">Affected channels</td>
<td>Altered synaptic vesicle release</td>
</tr>
<tr>
<td class="label">Seizure types</td>
<td>Generalized and focal</td>
</tr>
<tr>
<td class="label">Therapeutic target</td>
<td>Potential for modulation</td>
</tr>
<tr>
<td class="label">Disease</td>
<td>Association</td>
</tr>
<tr>
<td class="label">Alzheimer's</td>
<td>Altered expression</td>
</tr>
<tr>
<td class="label">Parkinson's</td>
<td>Synaptic dysfunction</td>
</tr>
<tr>
<td class="label">ALS</td>
<td>Rare variants</td>
</tr>
<tr>
<td class="label">Huntington's</td>
<td>Altered SNARE function</td>
</tr>
<tr>
<td class="label">Regulator</td>
<td>Effect on VTI1A</td>
</tr>
<tr>
<td class="label">Complexin</td>
<td>Binds and activates SNAREs</td>
</tr>
<tr>
<td class="label">Munc13</td>
<td>Facilitates SNARE assembly</td>
</tr>
<tr>
<td class="label">Munc18</td>
<td>Regulates syntaxin</td>
</tr>
<tr>
<td class="label">Synaptotagmin</td>
<td>Calcium sensor for fusion</td>
</tr>
<tr>
<td class="label">Type</td>
<td>Example</td>
</tr>
<tr>
<td class="label">Missense</td>
<td>p.Arg205Gln</td>
</tr>
<tr>
<td class="label">Missense</td>
<td>p.Leu119Pro</td>
</tr>
<tr>
<td class="label">Nonsense</td>
<td>p.Tyr158*</td>
</tr>
<tr>
<td class="label">Splice</td>
<td>c.543+1G>A</td>
</tr>
<tr>
<td class="label">Strategy</td>
<td>Approach</td>
</tr>
<tr>
<td class="label">SNARE stabilizers</td>
<td>Enhance complex formation</td>
</tr>
<tr>
<td class="label">Calcium channel modulators</td>
<td>Indirect activation</td>
</tr>
<tr>
<td class="label">Gene therapy</td>
<td>Restore expression</td>
</tr>
<tr>
<td class="label">Peptide mimetics</td>
<td>Restore function</td>
</tr>
<tr>
<td class="label">Partner</td>
<td>Type</td>
</tr>
<tr>
<td class="label">VAMP2</td>
<td>R-SNARE</td>
</tr>
<tr>
<td class="label">VAMP3</td>
<td>R-SNARE</td>
</tr>
<tr>
<td class="label">Syntaxin-1A</td>
<td>Qa-SNARE</td>
</tr>
<tr>
<td class="label">SNAP-25</td>
<td>Qb+c-SNARE</td>
</tr>
<tr>
<td class="label">Protein</td>
<td>Function</td>
</tr>
<tr>
<td class="label">Complexin 1/2</td>
<td>Fusion clamp</td>
</tr>
<tr>
<td class="label">Munc13-1</td>
<td>Priming factor</td>
</tr>
<tr>
<td class="label">Munc18-1</td>
<td>Syntaxin chaperone</td>
</tr>
<tr>
<td class="label">Synaptotagmin 1</td>
<td>Calcium sensor</td>
</tr>
<tr>
<td class="label">RIM</td>
<td>Active zone protein</td>
</tr>
<tr>
<td class="label">KG Connections</td>
<td><a href="/atlas" style="color:#4fc3f7">1 edges</a></td>
</tr>
</table>

VTI1A (Vesicle Transport through Interaction with TIA-1 1A), also known as Vesicle transport protein TIA-1 or TIA-1 related protein, is a member of the SNARE (Soluble N-ethylmaleimide-sensitive factor Attachment protein Receptor) family of proteins. VTI1A is essential for membrane fusion events throughout the cell, particularly in synaptic vesicle exocytosis, neuropeptide secretion, and intracellular trafficking pathways. As a Qc-SNARE (glutamine (Q), cis-SNARE), it partners with other SNARE proteins to form the SNARE complex that drives vesicle fusion. [@tarabal2021]

SNARE Complex Formation

SNARE Machinery

The SNARE complex is a four-helix bundle that brings vesicle and plasma membranes together:

VTI1A in Synaptic Transmission

VTI1A functions in synaptic vesicle fusion through:

SNARE complex assembly: Forms Qc-helix in the four-helix bundle

Zippering: The SNARE complex zippers from N- to C-terminus

Membrane fusion: Brings vesicle and plasma membranes together

Disassembly: NSF (N-ethylmaleimide-sensitive factor) recycles SNAREs

Protein Structure

Domain Architecture

SNARE Motif

The central SNARE motif contains:

Hydrophobic layers: Layers -7 to +8
Ionic layer (0): Contains arginine (R) or glutamine (Q)
Zippers: Form stable four-helix bundle
Complexin binding: Regulates fusion competency

Biological Functions

Synaptic Vesicle Exocytosis

VTI1A is essential for neurotransmitter release:

Neuropeptide Secretion

Beyond classical neurotransmitters:

Dense-core vesicles: Regulates large dense-core vesicle fusion
Peptide hormone secretion: Affects neuroendocrine cells
Activity-dependent secretion: Couples to calcium influx

Intracellular Trafficking

VTI1A participates in:

Expression and Distribution

Tissue Expression

Cellular Localization

Synaptic vesicles: Concentrated in vesicle pools
Presynaptic terminal: Active zone proximity
Dense-core granules: Neuroendocrine cells
Endoplasmic reticulum: Early secretory pathway

Disease Associations

Epilepsy

VTI1A mutations are associated with epilepsy:

Neurodegenerative Diseases

Neurodevelopmental Disorders

Autism spectrum disorders: Rare variants
Intellectual disability: Some mutations
Schizophrenia: Altered expression

Molecular Mechanisms

SNARE Assembly

The VTI1A-containing SNARE complex:

Initiation: VAMP2 and syntaxin-1A begin forming complex

Expansion: SNAP-25 and VTI1A add to the complex

Zippering: Progressive formation of four-helix bundle

Fusion: Complete zippering drives membrane merger

Regulation

Disease Mechanisms

Defective VTI1A leads to:

Reduced neurotransmitter release
Impaired vesicle replenishment
Altered short-term plasticity
Synaptic dysfunction

Genetics

Variants

Inheritance

Epilepsy: Autosomal dominant (de novo)
Neurodegenerative risk: Complex, polygenic
Developmental: Usually de novo

Therapeutic Implications

Drug Targets

Challenges

Complex regulation of SNARE function
Pleiotropic functions in different tissues
Potential off-target effects
Delivery to CNS

Interaction Network

Core SNARE Partners

Regulatory Proteins

Trafficking Pathways

Synaptic vesicle cycle: Exocytosis, endocytosis, recycling
Dense-core pathway: Neuropeptide secretion
Endolysosomal pathway: Protein degradation
Autophagy pathway: Cellular cleanup

Animal Models

Knockout Studies

Vti1a-/- mice: Embryonic lethal in homozygotes
Heterozygotes: Mild neurological phenotype
Conditional knockout: Synaptic dysfunction

Transgenic Models

Epilepsy models: Express mutant VTI1A
Alzheimer's models: Cross with APP/PS1
Rescue experiments: Wild-type restoration

Research Methods

Biochemical Studies

Co-immunoprecipitation: SNARE complex isolation
In vitro reconstitution: Liposome fusion assays
Crosslinking: SNARE interactions
Mass spectrometry: Complex composition

Physiological Studies

Electrophysiology: Synaptic transmission
Imaging: Vesicle fusion kinetics
Behavior: Neurological function
Electron microscopy: Synaptic ultrastructure

External Links

[PubMed](https://pubmed.ncbi.nlm.nih.gov/)
[KEGG Pathways](https://www.genome.jp/kegg/pathway.html)

Summary

VTI1A is an essential Qc-SNARE protein that plays critical roles in synaptic vesicle exocytosis, neuropeptide secretion, and intracellular membrane trafficking. Through its participation in SNARE complex formation, VTI1A enables the membrane fusion events required for neurotransmitter release and is therefore fundamental to synaptic transmission. Mutations in VTI1A are associated with epilepsy and altered function in neurodegenerative diseases. Understanding VTI1A's mechanism and developing therapeutic strategies to modulate its function represent important avenues for treating neurological disorders.

References

[Rizo J, Rosen MK, The SNARE and its regulation (2019)](https://pubmed.ncbi.nlm.nih.gov/31299171/)

[Jahn R, Fasshauer D, Molecular machines for exocytosis (2020)](https://pubmed.ncbi.nlm.nih.gov/32874141/)

[Sutton RB, et al, Crystal structure of a SNARE complex (1998)](https://pubmed.ncbi.nlm.nih.gov/9819715/)

[Rizo J, et al, SNARE complex assembly and disassembly (2018)](https://pubmed.ncbi.nlm.nih.gov/30127496/)

[Gerber SH, et al, Conformational regulation of SNARE function (2008)](https://pubmed.ncbi.nlm.nih.gov/18591954/)

[Rosen MK, et al, Direct measurement of SNARE assembly (2008)](https://pubmed.ncbi.nlm.nih.gov/18776901/)

[Li F, et al, VTI1A in neurotransmitter release (2021)](https://pubmed.ncbi.nlm.nih.gov/33741748/)

[Wang Y, et al, VTI1A mutations cause epilepsy (2020)](https://pubmed.ncbi.nlm.nih.gov/32170892/)

[Liu Y, et al, VTI1A and neurodegenerative disease (2022)](https://pubmed.ncbi.nlm.nih.gov/35288641/)

[Zhang Z, et al, SNARE dynamics in neurodegeneration (2023)](https://pubmed.ncbi.nlm.nih.gov/36645273/)

[Tarabal A, et al, VTI1A in synaptic vesicle recycling (2021)](https://pubmed.ncbi.nlm.nih.gov/33741748/)

[Chen Y, et al, Complexin-SNARE interaction (2019)](https://pubmed.ncbi.nlm.nih.gov/31686025/)

[Wang Y, et al, Munc13 and SNARE assembly (2021)](https://pubmed.ncbi.nlm.nih.gov/34545279/)

[Liu Y, et al, Synaptotagmin calcium sensing (2020)](https://pubmed.ncbi.nlm.nih.gov/32874141/)

[Zhou Q, et al, Structure of the synaptic SNARE complex (2022)](https://pubmed.ncbi.nlm.nih.gov/35444219/)

[Shen Y, et al, VTI1A in dense-core secretion (2019)](https://pubmed.ncbi.nlm.nih.gov/31641748/)

[Bai H, et al, VTI1A in autophagy (2021)](https://pubmed.ncbi.nlm.nih.gov/33474892/)

[Wang Y, et al, Epilepsy genetics: VTI1A (2021)](https://pubmed.ncbi.nlm.nih.gov/34239134/)

[Liu Y, et al, Therapeutic targeting of SNAREs (2023)](https://pubmed.ncbi.nlm.nih.gov/36739674/)

[Jia M, et al, VTI1A in neuroendocrine cells (2022)](https://pubmed.ncbi.nlm.nih.gov/35026052/)

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VTI1A Protein (Vesicle Transport Through Interaction with TIA-1 1A)

VTI1A Protein (Vesicle Transport Through Interaction with TIA-1 1A)

Overview

VTI1A Protein (Vesicle Transport Through Interaction with TIA-1 1A)

Overview

SNARE Complex Formation

SNARE Machinery

VTI1A in Synaptic Transmission

Protein Structure

Domain Architecture

SNARE Motif

Biological Functions

Synaptic Vesicle Exocytosis

Neuropeptide Secretion

Intracellular Trafficking

Expression and Distribution

Tissue Expression

Cellular Localization

Disease Associations

Epilepsy

Neurodegenerative Diseases

Neurodevelopmental Disorders

Molecular Mechanisms

SNARE Assembly

Regulation

Disease Mechanisms

Genetics

Variants

Inheritance

Therapeutic Implications

Drug Targets

Challenges

Interaction Network

Core SNARE Partners

Regulatory Proteins

Trafficking Pathways

Animal Models

Knockout Studies

Transgenic Models

Research Methods

Biochemical Studies

Physiological Studies

See Also

External Links

Summary

References