ACTC1 - Actin Alpha 1 Cardiac Muscle | Elisa - Clia - Antibody - Protein

Background

ACTC1 encodes for actin alpha 1, a protein that is a crucial component of the contractile apparatus in cardiac muscle cells (cardiomyocytes).  It is a major component of the contractile apparatus in cardiac muscle cells, contributing to the contraction and relaxation of the heart. It forms filamentous structures that, along with other proteins such as myosin, tropomyosin, and troponin, make up the sarcomeres—the basic contractile units of cardiac muscle. The contraction of cardiac muscle is regulated by calcium-dependent signaling pathways that modulate the interaction between actin and myosin. During each heartbeat, calcium ions bind to troponin, leading to conformational changes that expose binding sites on actin, allowing myosin to interact and generate force for muscle contraction. The expression of ACTC1 is highly regulated during cardiac development and in response to physiological and pathological stimuli. Mutations in the ACTC1 gene have been associated with various congenital heart diseases, such as hypertrophic cardiomyopathy (HCM) and dilated cardiomyopathy (DCM), which are characterized by abnormalities in cardiac muscle structure and function.

Protein Structure

Actin alpha 1 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 filament stability.
• High Affinity Binding Sites for Myosin: Crucial for muscle contraction through interaction with myosin heads during the cross-bridge 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, ACTC1 in cardiac muscle).
• Beta and Gamma Actins: Predominantly found in non-muscle cells (ACTB, ACTG1).

ACTC1 specifically refers to the alpha actin isoform expressed in cardiac muscle.

Function and Biological Significance

ACTC1 plays several critical roles in cardiac muscle function:

1. Muscle Contraction: Forms the core of the thin filaments in cardiac muscle fibers, interacting with myosin to facilitate contraction.
2. Structural Support: Provides mechanical support and maintains the structural integrity of cardiac muscle cells.
3. Force Transmission: Plays a role in the transmission of contractile force across the cardiac muscle tissue.
4. Cell Motility: Involved in the migration of cardiac cells during heart development and repair.
5. Regulation of Heart Function: Involved in processes that regulate heart muscle contraction and relaxation.

Interactions

ACTC1 interacts with a variety of proteins and molecular pathways:

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

Clinical Significance

Mutations or dysregulation of ACTC1 can lead to several cardiac disorders:

1. Hypertrophic Cardiomyopathy (HCM): Mutations in ACTC1 can cause HCM, characterized by abnormal thickening of the heart muscle, leading to impaired function and risk of sudden cardiac death.
2. Dilated Cardiomyopathy (DCM): Mutations can also cause DCM, where the heart becomes enlarged and weakened, leading to heart failure.
3. Idiopathic Restrictive Cardiomyopathy (IRC): ACTC1 mutations are implicated in this rare condition, where the heart muscle becomes rigid and restricts normal filling of the heart chambers.
4. Congenital Heart Defects: Abnormalities in ACTC1 expression can contribute to various congenital heart diseases.
5. Arrhythmias: Dysfunction in actin-mediated force transmission can lead to irregular heart rhythms.

Summary

ACTC1 encodes actin alpha 1, a protein essential for the structure and function of cardiac muscle. It forms the thin filaments of cardiac muscle fibers, interacts with myosin to facilitate contraction, and provides structural integrity to heart cells. Mutations in ACTC1 can lead to various cardiac disorders, including hypertrophic cardiomyopathy, dilated cardiomyopathy, and idiopathic restrictive cardiomyopathy. Understanding the structure, function, interactions, and clinical implications of ACTC1 provides valuable insights into its role in cardiac muscle biology and potential therapeutic targets for heart diseases.