ADAM23 - ADAM metallopeptidase domain 23 | Elisa - Clia - Antibody - Protein

Background

ADAM23 (A Disintegrin And Metalloproteinase domain-containing protein 23) is a member of the ADAM family of proteins, which are transmembrane proteins with diverse functions including cell adhesion, migration, proteolysis, and signaling. The ADAM family is characterized by the presence of a conserved metalloproteinase domain, which is responsible for their proteolytic activity, as well as other functional domains such as disintegrin, cysteine-rich, transmembrane, and cytoplasmic domains. ADAM23 specifically is known to play roles in neuronal development and function. It is predominantly expressed in the nervous system, particularly in the brain, including regions such as the cerebellum, cerebral cortex, hippocampus, and olfactory bulb. Within these regions, ADAM23 is involved in processes such as neurite outgrowth, axon guidance, synaptogenesis, and synaptic plasticity. ADAM23 may function as a receptor for various extracellular matrix proteins and cell adhesion molecules, allowing it to mediate interactions between neurons and their surrounding environment. Additionally, ADAM23 has been implicated in neurodevelopmental disorders and neurological diseases, although the precise mechanisms are not fully understood.

Protein Structure

ADAM23 has a complex multi-domain structure characteristic of the ADAM family:

• Signal Peptide: Directs the nascent protein to the secretory pathway.
• Prodomain: Maintains the enzyme in an inactive form until it is cleaved off to activate the enzyme.
• Metalloprotease Domain: Contains the catalytic site with a zinc-binding motif, although ADAM23 is considered catalytically inactive due to mutations that render the metalloprotease domain non-functional.
• Disintegrin Domain: Facilitates interactions with integrins and other cell surface receptors, contributing to cell adhesion.
• Cysteine-Rich Domain: Contributes to the protein’s stability and interactions.
• EGF-Like Domain: Involved in protein-protein interactions.
• Transmembrane Domain: Anchors the protein in the cell membrane.
• Cytoplasmic Tail: Participates in intracellular signaling and interactions with cytoskeletal elements.

Classification and Subtypes

ADAM23 belongs to the ADAM family, which includes proteins with metalloprotease and disintegrin domains. Despite having a metalloprotease domain, ADAM23 is classified as a non-proteolytic ADAM protein due to its lack of protease activity.

Function and Biological Significance

ADAM23 is involved in several critical biological functions:

1. Neuronal Development: Plays a vital role in the development and function of the nervous system.
2. Synaptic Function: Important for synapse formation and maintenance, contributing to neuronal communication.
3. Cell Adhesion: The disintegrin domain facilitates interactions with integrins, promoting cell-cell and cell-matrix adhesion.
4. Signal Transduction: Participates in signaling pathways that regulate neural plasticity and synaptic transmission.

Interactions

ADAM23 interacts with various proteins and cellular components:

1. LGI1: Interacts with the leucine-rich glioma inactivated 1 (LGI1) protein, which is critical for synaptic function and is implicated in epilepsy.
2. Integrins: The disintegrin domain mediates interactions with integrins, affecting cell adhesion and signaling.
3. Neurexins and Neuroligins: May interact with these synaptic cell adhesion molecules, influencing synapse formation and function.
4. Cytoskeletal Proteins: The cytoplasmic tail interacts with cytoskeletal elements, contributing to cell structure and signaling.

Clinical Significance

The function and regulation of ADAM23 have significant implications in various neurological conditions:

1. Epilepsy: Mutations in ADAM23 or its interacting partners, like LGI1, are associated with epilepsy and other seizure disorders.
2. Neurodevelopmental Disorders: Abnormalities in ADAM23 function can lead to neurodevelopmental issues, impacting learning and memory.
3. Neurodegenerative Diseases: Dysregulation of ADAM23 may be involved in the pathogenesis of neurodegenerative diseases such as Alzheimer's disease.
4. Cancer: Though primarily expressed in the nervous system, aberrant expression of ADAM23 has been implicated in certain cancers.

Summary

ADAM23, a member of the ADAM family, is crucial for neural development and synaptic function. Although it contains a metalloprotease domain, it is catalytically inactive, functioning primarily through its disintegrin domain to mediate cell adhesion and signaling. ADAM23 interacts with proteins such as LGI1, integrins, neurexins, and neuroligins. Clinically, ADAM23 is significant in the context of epilepsy, neurodevelopmental disorders, neurodegenerative diseases, and cancer. Understanding its structure, function, interactions, and clinical implications provides valuable insights into its role in the nervous system and potential as a therapeutic target.