DOCK3 Antibody, HRP conjugated
Description
Molecular and Functional Characteristics
Target Protein: DOCK3 (Dedicator of Cytokinesis 3), also known as MOCA or PBP, is a 233 kDa cytoplasmic protein involved in neuronal signaling, cytoskeletal regulation, and muscle health . It functions as a guanine nucleotide exchange factor (GEF) for Rac1, modulating cell adhesion, axonal outgrowth, and synaptic plasticity .
Antibody Properties:
-
Conjugate: HRP enzyme covalently linked via Lightning-Link® or similar kits .
-
Reactivity: Human, with cross-reactivity reported in mouse and rat tissues .
2.1. Neurodevelopmental Studies
DOCK3 is critical in neuronal health, and its dysregulation is linked to neurodevelopmental disorders. The HRP-conjugated antibody has been used to:
-
Detect DOCK3 in Alzheimer’s disease brain tissues, particularly in neurofibrillary tangles .
-
Study interactions with NMDA receptor subunits (e.g., NR2D) to elucidate neuroprotective mechanisms .
2.2. Muscle Physiology
Recent studies highlight DOCK3’s role in skeletal muscle regulation. Knockdown experiments in Duchenne muscular dystrophy (DMD) models showed improved myogenic fusion, suggesting therapeutic potential .
2.3. Signaling Pathways
-
GPCR Pathways: DOCK3 modulates G-protein-coupled receptor signaling via Rac1 activation .
-
JNK Inhibition: Acts as a negative regulator in B-cell signaling through interactions with INPP5D/SHIP1 .
3.1. Western Blot Performance
3.2. Immunohistochemistry
-
Optimal staining achieved in formaldehyde-fixed paraffin-embedded sections using antigen retrieval (TE buffer, pH 9.0) .
-
Localizes DOCK3 to neuronal cytoplasm and dystrophic muscle fibers .
4.1. Interaction with NMDA Receptors
Co-immunoprecipitation studies confirmed DOCK3 binds NR2D subunits in HEK293T cells and embryonic mouse brains . This interaction protects retinal ganglion cells from glutamate-induced apoptosis .
4.2. Therapeutic Implications
-
DMD Models: DOCK3 knockdown enhanced myotube formation in human DMD myoblasts, independent of dystrophin .
-
Neuroprotection: Overexpression of DOCK3 in neurons inhibits amyloid-beta accumulation, a hallmark of Alzheimer’s pathology .
Conjugation and Optimization
HRP conjugation kits (e.g., Lightning-Link®) enable efficient labeling with:
Product Specs
Constituents: 50% Glycerol, 0.01M PBS, pH 7.4
Target Background
- This study reports a second case of biallelic DOCK3 mutation caused by homozygous deletion. Considering the clinical similarities among cases with DOCK3 mutations, this finding further strengthens the evidence that biallelic mutations of DOCK3 contribute to a specific DOCK3-related neurodevelopmental syndrome. PMID: 29130632
- Common features observed in both affected individuals include severe developmental disability, ataxic gait, and severe hypotonia, closely resembling the phenotype observed in Dock3 knockout mice. This research demonstrates that complete DOCK3 deficiency in humans leads to developmental disability characterized by significant hypotonia and gait ataxia, likely due to abnormal axonal development. PMID: 28195318
- Inhibition of Dock3 using Dock3 shRNA mitigated the severity of status epilepticus in the acute stage and reduced the frequency of spontaneous recurrent seizures in the chronic stage of the lithium-pilocarpine model. This effect was associated with decreased expression of rac1-GTP. PMID: 26319681
- The findings suggest that miR-512-3p can inhibit tumor cell adhesion, migration, and invasion by regulating RAC1 activity through DOCK3 in NSCLC A549 and H1299 cell lines. PMID: 25687035
- DOCK3 plays a significant role in axonal regeneration. (review) PMID: 22746061
- MOCA is a pivotal molecule in Alzheimer's disease-relevant neuronal death signals, connecting the presenilin-mediated death signal with the APP-mediated death signal at a point between Rac1 or Cdc42 and ASK1. PMID: 22115042
- DOCK3 promotes axonal outgrowth by stimulating membrane recruitment of the WAVE complex. PMID: 20368433
- This research reveals that MOCA modulates cell-cell adhesion and morphology by increasing the accumulation of adherens junction proteins. PMID: 15647471
- MOCA is a novel Wnt negative regulator, demonstrating that this screening approach can be a rapid method for identifying new Wnt regulators. PMID: 18716063
