GABARAPL1 Human
Description
Structure and Functional Overview of GABARAPL1 Human
GABARAPL1 (Gamma-Aminobutyric Acid Receptor-Associated Protein-Like 1) is a ubiquitously expressed protein encoded by the GABARAPL1 gene located on human chromosome 12 . It belongs to the Atg8 family, sharing 87% amino acid identity with GABARAP and functioning as a critical autophagy-related protein .
Autophagy and Cellular Homeostasis
GABARAPL1 regulates autophagic flux by tagging autophagosomes, enabling their fusion with lysosomes . It also interacts with tubulin and microtubules, influencing cytoskeletal dynamics and mitochondrial homeostasis .
Synaptic Receptor Trafficking
GABARAPL1 stabilizes GABA(A) receptors at synapses by promoting their trafficking rather than inhibiting endocytosis . This interaction is mediated through a conserved region in the γ2 subunit, as revealed by crystallographic studies .
Metabolic Regulation
-
Mitochondrial Turnover: Facilitates mitophagy by interacting with BNIP3L, preventing mitochondrial damage accumulation .
-
Energy Metabolism: Downregulation increases basal oxygen consumption and ATP levels, potentially driving cancer progression .
Cancer Prognostics
GABARAPL1 expression exhibits context-dependent roles:
Mechanistic Insights
-
Breast Cancer: Overexpression inhibits proliferation in MCF-7 cells, while knockdown enhances invasion and metastasis .
-
HCC: Low expression correlates with aggressive tumor behavior, potentially due to impaired autophagy and Wnt pathway deregulation .
Aminoglycoside-Induced Hearing Loss
GABARAPL1 and GABARAP are essential for aminoglycoside (AG)-induced hair cell death :
| Model | Observation |
|---|---|
| GABARAPL1 KO Mice | Partial protection against AG-induced hearing loss (~80% hair cell survival) |
| GABARAP KO Mice | Complete protection from AG ototoxicity (minimal hair cell loss) |
| AAV-Mediated RNAi | Targeted knockdown of Gabarap in the inner ear prevents hearing loss |
Breast Cancer Subtypes
-
Estrogen-Regulated Role: gabarapl1 mRNA is downregulated in estrogen receptor-negative tumors .
-
TNBC Pathogenesis: GABARAPL1 promotes metastasis via MTDH (metadherin) upregulation .
Molecular Techniques
Product Specs
MGSSHHHHHH SSGLVPRGSH MKFQYKEDHP FEYRKKEGEK IRKKYPDRVP VIVEKAPKAR VPDLDKRKYL VPSDLTVGQF YFLIRKRIHL RPEDALFFFV NNTIPPTSAT MGQLYEDNHE EDYFLYVAYS DESVYGK.
Product Science Overview
Gamma-aminobutyric acid (GABA) is the primary inhibitory neurotransmitter in the central nervous system (CNS). It plays a crucial role in regulating neuronal excitability throughout the nervous system. GABA exerts its effects through two main types of receptors: GABA(A) and GABA(B). Among these, GABA(A) receptors are ligand-gated chloride channels that mediate fast synaptic inhibition.
GABARAPL1 is a ubiquitin-like modifier that plays a significant role in the formation of autophagosomal vacuoles. It is involved in the elongation of the phagophore membrane and is essential for the maturation of autophagosomes . Additionally, GABARAPL1 increases the cell surface expression of kappa-type opioid receptors by facilitating their anterograde intracellular trafficking .
GABARAPL1 is implicated in several physiological processes, including the cellular response to nutrient starvation and the remodeling of subdomains of the endoplasmic reticulum into autophagosomes . Dysregulation of GABARAPL1 has been associated with various diseases, such as Joubert Syndrome 20 and sarcoma .
Recombinant GABARAPL1 is used in research to study its role in autophagy and intracellular trafficking. It is also utilized to understand its interactions with other proteins and its involvement in various cellular processes. The study of GABARAPL1 can provide insights into the mechanisms underlying neuropsychiatric disorders and other diseases associated with autophagy dysfunction .
