GABARAPL - GABA A Receptor Associated Protein Like Protein | Elisa - Clia - Antibody - Protein

Background:

Gamma-Aminobutyric Acid B Receptors (GABBRs) are a class of G protein-coupled receptors (GPCRs) that respond to the neurotransmitter gamma-aminobutyric acid (GABA), the primary inhibitory neurotransmitter in the central nervous system. GABBRs were first identified and characterized in the 1980s and 1990s through pharmacological and molecular studies. GABBRs mediate the effects of GABA, leading to inhibition of neurotransmitter release and neuronal excitability. GABBRs are primarily expressed in the central nervous system, particularly in regions involved in synaptic transmission and neuronal excitability, such as the cerebral cortex, hippocampus, basal ganglia, and cerebellum. GABBRs are activated by the neurotransmitter GABA, which binds to the GABBR1 subunit. Several synthetic ligands, including agonists and antagonists, have been developed to selectively modulate GABBR activity for therapeutic purposes.GABBRs play crucial roles in regulating synaptic transmission, neuronal excitability, and synaptic plasticity in the central nervous system. Dysregulation of GABBR signaling is implicated in various neurological and psychiatric disorders

GABARAPL (GABA A Receptor Associated Protein Like Protein) is a member of the Atg8 (autophagy-related 8) protein family, which is involved in autophagy, a cellular degradation process crucial for maintaining cellular homeostasis. GABARAPL plays a significant role in the transport and function of GABA A receptors, which are important for inhibitory neurotransmission in the central nervous system (CNS). Additionally, GABARAPL is involved in various other cellular processes, including membrane trafficking, immune response, and protein degradation.

Structural Features

GABARAPL is a ubiquitin-like protein characterized by:

• Ubiquitin-like Fold: The protein has a similar structure to ubiquitin, which allows it to interact with other proteins and lipids.
• C-terminal Glycine: This residue is critical for conjugation to phosphatidylethanolamine (PE) during the autophagy process.
• LIR (LC3-interacting region) Motif: Facilitates interaction with autophagy receptors and other proteins involved in the autophagic process.

Subtypes and Classification

GABARAPL belongs to the Atg8 family, which includes several subtypes:

• GABARAP (GABA Type A Receptor-Associated Protein): Closely related and often studied together with GABARAPL due to functional similarities.
• GABARAPL1 (GABARAP-like 1): Another family member with roles in autophagy and intracellular transport.
• GABARAPL2 (GATE-16): Involved in autophagy and membrane trafficking, especially in the Golgi apparatus.
• MAP1LC3 (Microtubule-associated proteins 1A/1B light chain 3): Includes LC3A, LC3B, and LC3C, which are crucial for autophagosome formation.

Ligands and Interactions

GABARAPL interacts with various ligands and proteins:

• Phosphatidylethanolamine (PE): Conjugates to GABARAPL during autophagy, anchoring it to autophagic membranes.
• GABA A Receptors: Interacts with these receptors, affecting their intracellular trafficking and surface expression.
• Atg Proteins: Collaborates with other autophagy-related proteins to facilitate autophagosome formation.
• Protein Kinases: Interaction with kinases can modulate its activity and function in autophagy and other processes.

Physiological Functions

GABARAPL is involved in several critical physiological functions:

• Autophagy: Plays a vital role in the formation of autophagosomes, the double-membrane vesicles that engulf cellular components for degradation.
• GABA A Receptor Trafficking: Influences the transport and surface expression of GABA A receptors, impacting inhibitory neurotransmission.
• Membrane Trafficking: Involved in various aspects of intracellular membrane trafficking, including vesicle transport and fusion.
• Immune Response: Participates in the regulation of immune responses, including the degradation of intracellular pathogens.

Clinical Implications

Dysfunction or alterations in GABARAPL expression or activity are associated with several clinical conditions:

• Neurodegenerative Diseases: Impaired autophagy and GABA A receptor trafficking can contribute to conditions like Parkinson's disease and Alzheimer's disease.
• Epilepsy: Altered GABA A receptor function due to GABARAPL dysfunction can lead to seizures and epilepsy.
• Cancer: Dysregulated autophagy involving GABARAPL can contribute to cancer progression and resistance to therapy.
• Immune Disorders: Aberrant GABARAPL function can impact immune responses and is implicated in autoimmune diseases.