Unc13a Antibody
Description
Introduction to UNC13A Antibody
UNC13A antibodies are specialized immunological tools designed to detect and study the UNC13A protein (Unc-13 homolog A), a critical synaptic regulator involved in neurotransmitter release. These antibodies target UNC13A, a 193-210 kDa protein encoded by the UNC13A gene, which plays essential roles in priming synaptic vesicles for exocytosis at neuronal active zones . UNC13A antibodies are widely used in neuroscience research to investigate synaptic dysfunction in neurodegenerative diseases like amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) .
Role in Neurodegenerative Disease Research
UNC13A antibodies have become pivotal in studying TDP-43 proteinopathy, a hallmark of ALS and FTD. Key findings include:
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TDP-43 Depletion Link: Loss of TDP-43 function induces cryptic exon inclusion in UNC13A mRNA, leading to nonsense-mediated decay and reduced protein levels . This mechanism is strongly associated with synaptic dysfunction in ALS/FTD patients .
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Genetic Risk Factor: Homozygosity for the C-allele at rs12608932 in UNC13A correlates with shorter ALS survival and cognitive impairment .
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Therapeutic Target: Restoring UNC13A expression is a promising strategy to mitigate neurodegeneration in TDP-43-related diseases .
Applications in Experimental Models
UNC13A antibodies enable diverse experimental approaches:
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Western Blot (WB): Detects UNC13A in brain lysates (hippocampus, cortex) .
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Immunohistochemistry (IHC): Localizes UNC13A in neuronal active zones; optimal antigen retrieval requires TE buffer (pH 9.0) .
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Immunofluorescence (IF): Visualizes synaptic vesicle priming defects in TDP-43-depleted neurons .
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Functional Studies: Used to validate UNC13A cryptic exon inclusion in ALS patient-derived neurons .
Table 2: Major Suppliers of UNC13A Antibodies
Implications for Therapeutic Development
UNC13A antibodies are critical tools in preclinical research for ALS/FTD:
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Biomarker Potential: Quantifying UNC13A levels in cerebrospinal fluid could track disease progression .
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Gene Therapy: Antisense oligonucleotides targeting UNC13A cryptic exons are under investigation .
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Drug Screening: Antibodies facilitate high-throughput assays to identify compounds that restore UNC13A expression .
Product Specs
Target Background
Munc13-1 plays a crucial role in vesicle maturation during exocytosis, serving as a target for the diacylglycerol second messenger pathway. It is involved in neurotransmitter release by priming synaptic vesicles before fusion and participates in the activity-dependent replenishment of the readily releasable vesicle pool (RRP). Munc13-1 is essential for synaptic vesicle maturation in most excitatory/glutamatergic synapses, but not in inhibitory/GABA-mediated synapses. Furthermore, it facilitates neuronal dense-core vesicle fusion and regulates the location and efficiency of their synaptic release. Its functions extend to secretory granule priming in insulin secretion and plays a role in melanocyte dendrite formation.
Munc13-1 Function and Mechanisms: A Review of Key Findings
- Studies suggest an inhibitory role for Munc13-1 in antigen-induced mast cell degranulation, a process mediated by Munc13-4. (PMID: 29225210)
- Investigations using site-directed mutagenesis (W22A, W22K, W22D, W22Y, W22F) in Munc13-1 expressed in Neuro-2a cells revealed that the C1 domain translocates to internal membranes in response to phorbol ester, while the protein translocates to the plasma membrane. Trp-588 is critical for ligand binding and translocation. (PMID: 29244485)
- Structural analysis indicates that Munc13-1 bridges the vesicle and plasma membranes at the periphery of the membrane-membrane interface, providing key insights into neurotransmitter release mechanisms. (PMID: 28177287)
- Research supports a model where multiple Munc13 domains cooperate to coordinate synaptic vesicle docking, priming, and fusion. (PMID: 27213521)
- Two conserved residues (R151, I155) in the syntaxin-1 linker region have been identified as crucial for the Munc13-1 MUN domain interaction, essential for SNARE complex formation and synaptic vesicle priming. (PMID: 28137749)
- The crystal structure of the rat Munc13-1 MUN domain reveals an elongated, arch-shaped architecture composed of alpha-helical bundles, featuring a highly conserved hydrophobic pocket. (PMID: 26030875)
- The C-terminal module of Munc13-1 contributes significantly to its function, but full activity requires interaction with adjacent modules. (PMID: 22000513)
- The Munc13-1 MUN domain accelerates the transition from the syntaxin-1-Munc18-1 complex to the SNARE complex. (PMID: 21499244)
- Activation of the metabotropic glutamate receptor mGlu7 leads to phospholipase C activation, Munc13-1 translocation, and potentiation of glutamate release at cerebrocortical nerve terminals. (PMID: 20375012)
- During repeated action potentials, Ca(2+) and phosphatidylinositolphosphate binding to the Munc13 C(2)B domain enhance synaptic vesicle exocytosis, counteracting synaptic depression caused by vesicle depletion. (PMID: 20154707)
- Presynaptic silencing is associated with decreased levels of the priming proteins Munc13-1 and Rim1. (PMID: 20130189)
- Munc13-1 regulates insulin exocytosis. (PMID: 12871971)
- A conserved tryptophan residue within the munc13-1 C1 domain occludes the diacylglycerol/phorbol ester-binding site, requiring a significant conformational change for ligand binding. (PMID: 15667202)
- The Munc13-1 C(2)A domain forms homodimers, which compete with Munc13-1/RIM heterodimerization. (PMID: 16732694)
- Studies have reported the expression, purification, and characterization of critical Munc13-1 domains. (PMID: 17687497)
- Munc13 proteins may facilitate the assembly of syntaxin-1/SNAP-25 heterodimers, forming an acceptor complex for synaptobrevin. (PMID: 18201107)
- Munc13-1 is expressed in pancreatic islets during fetal development, and its deficiency is linked to decreased blood insulin levels in intrauterine growth restriction (IUGR). (PMID: 18787382)
