ACTA2 - Actin alpha 2 smooth muscle | Elisa - Clia - Antibody - Protein

Background

ACTA2 encodes actin alpha 2, a protein that is a key component of the contractile apparatus in smooth muscle cells. Smooth muscle alpha actin is a major component of the contractile apparatus in smooth muscle cells, contributing to the contractility and mechanical properties of various organs and tissues, including blood vessels, airways, and the gastrointestinal tract. ACTA2 (as with all the actins) is extremely highly conserved and found in nearly all mammals Is essential for physiological processes such as blood pressure regulation, airway tone, and peristalsis in the digestive system. It forms filamentous structures that interact with other proteins to generate force and facilitate muscle contraction. Various signaling pathways and transcription factors control the expression of ACTA2, ensuring its proper expression in smooth muscle cells. Mutations or dysregulation of ACTA2 expression have been associated with several smooth muscle-related disorders, including vascular diseases such as thoracic aortic aneurysms and dissections (TAAD), familial thoracic aortic aneurysms and dissections (FTAAD), and other vascular malformations. Understanding the role of smooth muscle alpha actin in these conditions is critical for developing targeted therapies and interventions.

Protein Structure

Actin alpha 2 has a highly conserved structure characterized by:

• G-Actin (Globular Actin): Monomeric form that polymerizes to form F-actin.
• F-Actin (Filamentous Actin): Polymerized form that constitutes the thin filaments of muscle fibers.
• ATP Binding Site: Essential for actin polymerization and stability.
• High Affinity Binding Sites for Myosin: Crucial for muscle contraction through interaction with myosin heads during the contraction cycle.

Classification and Subtypes

Actin proteins are classified into several isoforms based on their tissue distribution:

• Alpha Actins: Found in muscle tissues (ACTA1 in skeletal muscle, ACTA2 in smooth muscle).
• Beta and Gamma Actins: Predominantly found in non-muscle cells (ACTB, ACTG1).

ACTA2 specifically refers to the alpha actin isoform expressed in smooth muscle.

Function and Biological Significance

ACTA2 plays several critical roles in smooth muscle function:

1. Muscle Contraction: Forms the core of the thin filaments in smooth muscle cells, interacting with myosin to facilitate contraction.
2. Structural Support: Provides mechanical support and maintains the structural integrity of smooth muscle cells.
3. Cell Motility: Involved in processes such as cell migration and smooth muscle development.
4. Vascular Tone Regulation: Crucial for the regulation of blood vessel diameter and blood pressure.
5. Visceral Muscle Function: Important for the function of visceral organs like the intestines and bladder.

Interactions

ACTA2 interacts with a variety of proteins and molecular pathways:

1. Myosin: Directly interacts with myosin heads during the contraction cycle.
2. Tropomyosin and Caldesmon: Regulatory proteins that modulate actin-myosin interactions and control muscle contraction.
3. Actin-Binding Proteins: Such as calponin, which regulate actin polymerization and stability.
4. Structural Proteins: Including dystrophin and spectrin, which link actin filaments to the cell membrane and extracellular matrix.
5. Signaling Molecules: Involved in pathways that regulate smooth muscle contraction and relaxation.

Clinical Significance

Mutations or dysregulation of ACTA2 can lead to several smooth muscle disorders and cardiovascular diseases:

1. Familial Thoracic Aortic Aneurysm and Dissection (TAAD): Mutations in ACTA2 are associated with this condition, characterized by weakening of the aortic wall and risk of rupture.
2. Congenital Myopathies: Rarely, ACTA2 mutations can present with congenital muscle disorders affecting smooth muscle function.
3. Smooth Muscle Tumors: ACTA2 expression is used as a marker in diagnosing smooth muscle tumors, such as leiomyomas and leiomyosarcomas.
4. Vascular Disorders: Dysregulation of ACTA2 is implicated in various vascular diseases, including hypertension and atherosclerosis.
5. Asthma and Other Respiratory Conditions: Altered smooth muscle function due to ACTA2 abnormalities can contribute to conditions affecting airway constriction.

Summary

ACTA2 encodes actin alpha 2, a protein essential for the structure and function of smooth muscle. It forms the thin filaments of smooth muscle fibers, interacts with myosin to facilitate contraction, and provides structural integrity to smooth muscle cells. Mutations in ACTA2 can lead to various smooth muscle disorders, including familial thoracic aortic aneurysm and dissection, as well as contribute to vascular diseases and tumors. Understanding the structure, function, interactions, and clinical implications of ACTA2 provides valuable insights into its role in smooth muscle biology and potential therapeutic targets for related diseases.