The gamma-aminobutyric acid type A (GABA(A)) receptor-associated protein is a versatile adaptor protein playing an important role in intracellular vesicle trafficking, particularly in neuronal cells. We present the X-ray structure of the soluble form of human GABA(A) receptor-associated protein complexed with a high-affinity synthetic peptide at 1.3 A resolution. The data shed light on the probable binding modes of key interaction partners, including the GABA(A) receptor and the cysteine protease Atg4. The resulting models provide a structural background for further investigation of the unique biological properties of this protein.
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http://dx.doi.org/10.1016/j.jmb.2008.06.086 | DOI Listing |
Ecotoxicol Environ Saf
December 2024
Department of Physiology, School of Basic Medical Sciences, Jiangxi Medical College, Nanchang University, Nanchang 330006, PR China. Electronic address:
Acrylamide (ACR), a chemical extensively utilized in industry and food processing sectors, has been recognized for its potentially irreversible adverse effect on male reproductive system; however, the underlying mechanism remains elusive. Our study reveals that ACR markedly triggers oxidative stress-mediated autophagy and upregulates the expression of GABAA-receptor-associated protein like-1 (GABARAPL1). Intriguingly, overexpression of GABARAPL1 significantly induces autophagy, while its knockdown alleviates ACR-induced autophagic responses, underscoring its pivotal function.
View Article and Find Full Text PDFCancers (Basel)
September 2024
Department of Neurosurgery, University of North Carolina, Chapel Hill, NC 27599, USA.
In non-small cell lung cancer (NSCLC) treatment, radiotherapy responses are not durable and toxicity limits therapy. We find that AM-101, a synthetic benzodiazepine activator of GABA(A) receptor, impairs the viability and clonogenicity of both primary and brain-metastatic NSCLC cells. Employing a human-relevant ex vivo 'chip', AM-101 is as efficacious as docetaxel, a chemotherapeutic used with radiotherapy for advanced-stage NSCLC.
View Article and Find Full Text PDFJ Neurosci
August 2024
Djavad Mowafaghian Centre for Brain Health and Department of Psychiatry, University of British Columbia, Vancouver, British Columbia V6T 2B5, Canada
The mechanisms utilized by neurons to regulate the efficacy of phasic and tonic inhibition and their impacts on synaptic plasticity and behavior are incompletely understood. Cleft lip and palate transmembrane protein 1 (Clptm1) is a membrane-spanning protein that interacts with multiple γ-aminobutyric acid type A receptor (GABAR) subunits, trapping them in the endoplasmic reticulum and Golgi network. Overexpression and knock-down studies suggest that Clptm1 modulates GABAR-mediated phasic inhibition and tonic inhibition as well as activity-induced inhibitory synaptic homeostasis in cultured hippocampal neurons.
View Article and Find Full Text PDFSynapse
March 2024
Faculty of International Medicine, Department of Biophysics, University of Health Sciences, Istanbul, Turkey.
Epileptic seizures are seen as a result of changing excitability balance depending on the deterioration in synaptic plasticity in the brain. Neuroplastin, and its related molecules which are known to play a role in synaptic plasticity, neurotransmitter activities that provide balance of excitability and, different neurological diseases, have not been studied before in epilepsy. In this study, a total of 34 Sprague-Dawley male and female rats, 2 months old, weighing 250-300 g were used.
View Article and Find Full Text PDFUnlabelled: In non-small cell lung cancer (NSCLC) treatment, targeted therapies benefit only a subset of NSCLC, while radiotherapy responses are not durable and toxicity limits therapy. We find that a GABA(A) receptor activator, AM-101, impairs viability and clonogenicity of NSCLC primary and brain metastatic cells. Employing an 'chip', AM-101 is as efficacious as the chemotherapeutic docetaxel, which is used with radiotherapy for advanced-stage NSCLC.
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