APBA3 - Amyloid Beta Precursor Protein Binding Protein A3 | Elisa - Clia - Antibody - Protein

Background:

APBA3, also known as Amyloid Beta Precursor Protein Binding Protein A3, is another member of the amyloid-beta precursor protein-binding family. Like APBA2, APBA3 interacts with the cytoplasmic domain of the amyloid precursor protein (APP). APBA3, similar to APBA2, plays a role in regulating the processing of APP and the production of amyloid-beta peptide, which is implicated in the pathology of Alzheimer's disease. Additionally, APBA3 is involved in intracellular signaling pathways and synaptic function, contributing to neuronal communication and plasticity. Dysregulation of APBA3 function may also be associated with Alzheimer's disease progression, although further research is needed to fully understand its role in the disease. Studying APBA3 and its interactions with other proteins involved in Alzheimer's disease could provide valuable insights into the underlying molecular mechanisms and potential therapeutic targets for the condition.

Protein Structure:

• PTB Domain: The phosphotyrosine-binding (PTB) domain at the N-terminus is essential for binding to the intracellular domain of APP. This interaction is crucial for modulating APP processing.
• PDZ Domains: APBA3 contains multiple PDZ domains, which facilitate interactions with other proteins and help in forming multiprotein complexes involved in various signaling pathways.
• C-terminal Domain: The C-terminal region is involved in protein-protein interactions, contributing to the protein's role in intracellular signaling and trafficking.

Classification and Subtypes:

APBA3 belongs to the X11/Mint family of proteins, characterized by their PTB and PDZ domains. The family includes:

• APBA1 (X11): Primarily involved in synaptic function and APP processing.
• APBA2 (X11L): Also involved in synaptic function and known for its role in APP processing similar to APBA1.

Function and Biological Significance:

• APP Processing: APBA3 binds to the intracellular domain of APP, influencing its cleavage and the production of amyloid-beta peptides, which are critical in the context of Alzheimer's disease.
• Intracellular Signaling: Through its PDZ domains, APBA3 participates in various signaling pathways by forming complexes with other signaling molecules, impacting cellular processes such as vesicle trafficking, signal transduction, and protein sorting.
• Vesicle Trafficking: APBA3 is involved in the regulation of vesicle trafficking, a crucial process for neurotransmitter release and synaptic function.

Interactions:

• Amyloid Precursor Protein (APP): APBA3 interacts with APP through its PTB domain, playing a role in its intracellular trafficking and processing.
• Other Proteins: APBA3 interacts with various other proteins through its PDZ domains, forming complexes that are important for intracellular signaling and maintaining cellular homeostasis.

Clinical Issues:

• Alzheimer’s Disease: Due to its role in APP processing and amyloid-beta production, APBA3 is implicated in the pathogenesis of Alzheimer’s disease. Abnormalities in its function or expression can contribute to the pathological accumulation of amyloid-beta plaques in the brain.
• Neurodegenerative Disorders: Beyond Alzheimer’s, dysregulation of APBA3 may be involved in other neurodegenerative conditions where protein aggregation and synaptic dysfunction are common features.
• Cancer: Recent studies suggest a potential role of APBA3 in cancer, particularly in tumorigenesis and metastasis, possibly due to its involvement in intracellular signaling pathways.

Summary:

APBA3 is a multifunctional protein that plays a critical role in the nervous system, particularly in the processing of amyloid precursor protein (APP) and intracellular signaling. Its interaction with APP and involvement in amyloid-beta production link it to Alzheimer's disease, making it a significant protein in neurodegenerative research. Additionally, APBA3's role in vesicle trafficking and cellular signaling underscores its importance in maintaining cellular function and integrity. Understanding the full spectrum of APBA3's interactions and functions could provide further insights into its role in both normal physiology and disease states, including neurodegeneration and cancer.