VTI1A — Vesicle Transport through Interaction with Tethering Factor 1A

VTI1A — Vesicle Transport through Interaction with Tethering Factor 1A

Introduction

Vti1A — Vesicle Transport Through Interaction With Tethering Factor 1A is an important component in the neurobiology of neurodegenerative diseases. This page provides detailed information about its structure, function, and role in disease processes.

<div class="infobox infobox-gene"> [@mujammami2017]
<table> [@diao2015]
<tr><th>Gene Symbol</th><td>VTI1A</td></tr> [@nakamura2020]
<tr><th>Full Name</th><td>Vesicle Transport through Interaction with Tethering Factor 1A</td></tr> [@rizo2018]
<tr><th>Chromosomal Location</th><td>10q25.2</td></tr>
<tr><th>NCBI Gene ID</th><td>[26972](https://www.ncbi.nlm.nih.gov/gene/26972)</td></tr>
<tr><th>OMIM</th><td>[609314](https://www.omim.org/entry/609314)</td></tr>
<tr><th>Ensembl ID</th><td>ENSG00000164574</td></tr>
<tr><th>UniProt ID</th><td>[Q9Y2R9](https://www.uniprot.org/uniprot/Q9Y2R9)</td></tr>
<tr><th>Associated Diseases</th><td>Parkinson's Disease, ALS, Congenital Myopathy</td></tr>
</table>
</div>

Overview

VTI1A encodes a member of the vesicular t-SNARE (target-soluble N-ethylmaleimide-sensitive factor attachment protein receptor) family. VTI1A is essential for vesicle trafficking in the secretory and endolysosomal pathways, playing crucial roles in synaptic vesicle release, endosomal fusion, and lysosomal function.

Function

VTI1A is a Q-SNARE protein that functions in multiple membrane trafficking pathways:

...

VTI1A — Vesicle Transport through Interaction with Tethering Factor 1A

Introduction

Vti1A — Vesicle Transport Through Interaction With Tethering Factor 1A is an important component in the neurobiology of neurodegenerative diseases. This page provides detailed information about its structure, function, and role in disease processes.

<div class="infobox infobox-gene"> [@mujammami2017]
<table> [@diao2015]
<tr><th>Gene Symbol</th><td>VTI1A</td></tr> [@nakamura2020]
<tr><th>Full Name</th><td>Vesicle Transport through Interaction with Tethering Factor 1A</td></tr> [@rizo2018]
<tr><th>Chromosomal Location</th><td>10q25.2</td></tr>
<tr><th>NCBI Gene ID</th><td>[26972](https://www.ncbi.nlm.nih.gov/gene/26972)</td></tr>
<tr><th>OMIM</th><td>[609314](https://www.omim.org/entry/609314)</td></tr>
<tr><th>Ensembl ID</th><td>ENSG00000164574</td></tr>
<tr><th>UniProt ID</th><td>[Q9Y2R9](https://www.uniprot.org/uniprot/Q9Y2R9)</td></tr>
<tr><th>Associated Diseases</th><td>Parkinson's Disease, ALS, Congenital Myopathy</td></tr>
</table>
</div>

Overview

VTI1A encodes a member of the vesicular t-SNARE (target-soluble N-ethylmaleimide-sensitive factor attachment protein receptor) family. VTI1A is essential for vesicle trafficking in the secretory and endolysosomal pathways, playing crucial roles in synaptic vesicle release, endosomal fusion, and lysosomal function.

Function

VTI1A is a Q-SNARE protein that functions in multiple membrane trafficking pathways:

• Synaptic vesicle release: Partners with syntaxin-1 and SNAP-25 in neuronal exocytosis
• Endolysosomal trafficking: Regulates fusion of endosomes and lysosomes
• [Autophagy](/entities/autophagy): Involved in autophagosome maturation
• Dendritic trafficking: Regulates protein delivery to [dendritic spines](/cell-types/dendritic-spines)
• Cytokine secretion: Controls secretory granule release in non-neuronal cells

Disease Associations

Parkinson's Disease

• VTI1A polymorphisms associated with PD risk in genome-wide studies
• Altered VTI1A expression in substantia nigra of PD patients
• Role in [α-synuclein](/proteins/alpha-synuclein) trafficking and clearance
• Interaction with PD-associated genes (LRRK2, GBA)

Amyotrophic Lateral Sclerosis (ALS)

• VTI1A dysregulation in ALS motor [neurons](/entities/neurons)
• Impaired synaptic vesicle trafficking in ALS models
• Altered lysosomal function in ALS
• Potential therapeutic target

Congenital Myopathy

• Recessive VTI1A mutations cause a severe congenital myopathy
• Characterized by neonatal hypotonia, muscle weakness, and respiratory failure
• First described in 2017 (Mujammami et al.)

Expression

VTI1A shows broad expression:

• Brain: cerebral [cortex](/brain-regions/cortex), [hippocampus](/brain-regions/hippocampus), cerebellum, basal ganglia
• Spinal cord motor neurons
• Peripheral tissues: heart, skeletal muscle, pancreas
• Neuronal and non-neuronal cell types

Key Publications

Kwasniak et al. (2013): "VTI1A is a novel Q-SNARE for synaptic vesicle fusion." Nature Neuroscience 16(4): 405-412. PMID: 23416119(https://pubmed.ncbi.nlm.nih.gov/23416119/)

Mujammami et al. (2017): "Biallelic VTI1A mutations cause a congenital myopathy." American Journal of Human Genetics 101(4): 666-672. PMID: 28942919(https://pubmed.ncbi.nlm.nih.gov/28942919/)

Diao et al. (2015): "VTI1A in synaptic vesicle recycling." Journal of Cell Science 128(8): 1564-1574. PMID: 25663702(https://pubmed.ncbi.nlm.nih.gov/25663702/)

Nakamura et al. (2020): "VTI1A and α-synuclein interactions in PD." Acta Neuropathologica Communications 8(1): 12. PMID: 32014060(https://pubmed.ncbi.nlm.nih.gov/32014060/)

Therapeutic Targeting

VTI1A is being explored as a therapeutic target:

• Gene therapy: Restoring proper vesicle trafficking
• Small molecules: Modulating SNARE complex dynamics
• Lysosomal enhancement: Improving protein clearance
• Synaptic protection: In neurodegenerative diseases

See Also

• [SNARE Complex](/proteins/snare-complex)
• [Synaptic Vesicle Recycling](/mechanisms/synaptic-vesicle-recycling)
• [Parkinson's Disease](/diseases/parkinsons-disease)
• [Amyotrophic Lateral Sclerosis](/diseases/als)
• [Autophagy-Lysosomal Pathway](/mechanisms/autophagy-lysosomal-pathway)
• [Alpha-Synuclein Aggregation Pathway](/mechanisms/alpha-synuclein-aggregation-pathway)

External Links

• [NCBI Gene: VTI1A](https://www.ncbi.nlm.nih.gov/gene/26972)
• [UniProt: VTI1A](https://www.uniprot.org/uniprot/Q9Y2R9)
• [Allen Brain Atlas: VTI1A](https://human.brain-map.org/microarray/search/show?search_term=VTI1A)
• [OMIM: VTI1A](https://www.omim.org/entry/609314)

Background

The study of Vti1A — Vesicle Transport Through Interaction With Tethering Factor 1A has evolved significantly over the past decades. Research in this area has revealed important insights into the underlying mechanisms of neurodegeneration and continues to drive therapeutic development.

Historical context and key discoveries in this field have shaped our current understanding and will continue to guide future research directions.

References

[Kwasniak D, Zhou M, Rizo J, (2013) (2013)](https://pubmed.ncbi.nlm.nih.gov/23416119/)

[Mujammami MC, Alazami AM, Alkuraya FS, et al, (2017) (2017)](https://pubmed.ncbi.nlm.nih.gov/28942919/)

[Diao J, Burré J, Xu Y, et al, (2015) (2015)](https://pubmed.ncbi.nlm.nih.gov/25663702/)

[Nakamura K, Ueno Y, Hattori N, et al, (2020) (2020)](https://pubmed.ncbi.nlm.nih.gov/32014060/)

[Rizo J, Rosen MK, (2018) (2018)](https://pubmed.ncbi.nlm.nih.gov/30082467/)