ACTG - Actin Gamma | Elisa - Clia - Antibody - Protein

Background

ACTG encodes gamma-actin, one of the six highly conserved actin isoforms present in eukaryotic cells. Gamma-actin is predominantly found in non-muscle cells and is essential for various cellular processes, including maintenance of the cytoskeleton, cell shape, motility, and intracellular transport. Gamma-actin is critical for cellular integrity and function across a wide range of tissues.Human gamma-actin, with a molecular weight of 41.8 kDa and consisting of 375 amino acids, is widely distributed in the cytoskeletons of various tissues. Within adult striated muscle cells, gamma-actin localizes predominantly to Z-discs and costamere structures, crucial for the transmission and transduction of force in muscle cells. Mutations in the ACTG1 gene, which encodes gamma-actin, have been implicated in several conditions. These include nonsyndromic hearing loss and Baraitser-Winter syndrome. Additionally, there's a noted susceptibility among adolescent patients with ACTG1 mutations to vincristine toxicity. Understanding the role of gamma-actin and its genetic variants is paramount in elucidating the pathophysiology of these conditions and in developing targeted therapeutic interventions.

Protein Structure

Gamma-actin has a highly conserved structure characterized by:

• G-Actin (Globular Actin): The monomeric form that can polymerize to form F-actin.
• F-Actin (Filamentous Actin): The polymerized form that constitutes the actin filaments within the cell.
• ATP Binding Site: Essential for actin polymerization and filament stability.
• High Affinity Binding Sites for Actin-Binding Proteins: Crucial for interactions with other cytoskeletal proteins and regulation of actin dynamics.

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).

ACTG specifically refers to the gamma actin isoform, which is ubiquitously expressed in various cell types but predominantly in non-muscle cells.

Function and Biological Significance

Gamma-actin plays several critical roles in cellular function:

1. Cytoskeleton Maintenance: Provides structural support to the cell, maintaining its shape and integrity.
2. Cell Motility: Involved in cell movement through processes such as lamellipodia and filopodia formation.
3. Intracellular Transport: Facilitates the movement of organelles, vesicles, and other cellular components.
4. Cell Division: Plays a key role during cytokinesis, the final stage of cell division.
5. Cell Signaling: Participates in signaling pathways that regulate cell growth, differentiation, and response to external stimuli.

Interactions

Gamma-actin interacts with a variety of proteins and molecular pathways:

1. Actin-Binding Proteins: Such as profilin, cofilin, and thymosin, which regulate actin polymerization and depolymerization.
2. Motor Proteins: Such as myosins, which use actin filaments as tracks for intracellular transport.
3. Cytoskeletal Proteins: Including spectrin and dystrophin, which link actin filaments to the cell membrane.
4. Signaling Molecules: Involved in pathways that regulate actin dynamics and cell motility.
5. Transcription Factors: Gamma-actin can influence gene expression by interacting with transcription factors and nuclear components.

Clinical Significance

Alterations or dysregulation of ACTG can lead to several disorders and diseases:

1. Hearing Loss: Mutations in ACTG1, the gene encoding gamma-actin, are associated with autosomal dominant non-syndromic hearing loss (DFNA20/26).
2. Cancer: Aberrant regulation of gamma-actin expression and actin cytoskeleton dynamics is implicated in cancer cell migration, invasion, and metastasis.
3. Developmental Disorders: Mutations in ACTG can lead to a variety of developmental abnormalities affecting multiple tissues and organ systems.
4. Cytoskeletal Disorders: Abnormalities in gamma-actin can lead to defects in cell shape and motility, contributing to various pathological conditions.

Summary

ACTG encodes gamma-actin, a protein essential for the structural integrity and function of non-muscle cells. Gamma-actin forms the cytoskeleton, supports cell motility, facilitates intracellular transport, and regulates cell signaling. Mutations in ACTG1 can lead to hearing loss and other developmental disorders, while its dysregulation is implicated in cancer and other diseases. Understanding the structure, function, interactions, and clinical implications of gamma-actin provides valuable insights into its role in cellular biology and potential therapeutic targets for related diseases.