Disease relevance of GABARAPL1

• Differential effects of thrombin and hypoxia on endometrial stromal and glandular epithelial cell vascular endothelial growth factor expression [1].

High impact information on GABARAPL1

• This pathway was of functional relevance, because targeting of the influenza matrix protein 1 to autophagosomes via fusion to the autophagosome-associated protein Atg8/LC3 led to strongly enhanced MHC class II presentation to CD4(+) T cell clones [2].
• Inhibition of autophagy by chemical compounds or knocking down the expression of key autophagy proteins such as ATG7, ATG8, and receptor interacting protein (RIP) blocks ROS accumulation and cell death [3].
• When expressed in Chinese hamster ovary (CHO) cells, GEC1 co-immunoprecipitated with FLAG-hKOR [4].
• The interaction with NSF may contribute to GEC1 effects [4].
• Phosphatidylserine in addition to phosphatidylethanolamine is an in vitro target of the mammalian Atg8 modifiers, LC3, GABARAP, and GATE-16 [5].

Biological context of GABARAPL1

• Screening of a guinea-pig genomic library led to identification of gec1 gene consisting of 4 exons and 3 introns [6].
• In this study, we combined brain dissection and quantitative real-time reverse transcription polymerase chain reaction to study discriminatively gabarap, gec1/gabarapL1, gate16/gabarapL2, lc3 mRNA distribution in multiple rat brain areas [7].
• In yeast, phosphatidylethanolamine is a target of the Atg8 modifier in ubiquitylation-like reactions essential for autophagy [5].
• GEC1 expression slightly reduced U50,488H-promoted down-regulation, without affecting ligand binding affinity, receptor-G protein coupling, or U50,488H-induced desensitization and internalization [4].
• This domain is thought to be the binding site for Atg8 homologs [8].

Anatomical context of GABARAPL1

• The expression levels of GABARAPL1 as a 2.3-kb transcript were very high in brain, heart, peripheral blood leukocytes, liver, kidney, placenta, and skeletal muscle, very low in thymus and small intestine, and moderate in other tissues tested [9].
• Guinea-pig and human gec1/GABARAPL1 proteins share 87% identity with GABARAP, which acts as a protein linker between microtubules and the GABA(A) receptor [10].
• HA-GEC1 expressed in CHO cells was localized in the Golgi apparatus and endoplasmic reticulum (ER) [4].
• The lipidated Atg8 and LC3 localize to autophagosomal membranes and play indispensable roles for maturation of autophagosomes [11].
• GEC1 was present in all rat brain regions examined and spinal cord [12].

Associations of GABARAPL1 with chemical compounds

• Analysis of the guinea-pig estrogen-regulated gec1/GABARAPL1 gene promoter and identification of a functional ERE in the first exon [10].
• Each purified mutant Atg8 homolog with an exposed C-terminal Gly formed an E1-substrate intermediate with hAtg7 via a thioester bond in an ATP-dependent manner and formed an E2-substrate intermediate with hAtg3 via a thioester bond dependent on ATP and hAtg7 [5].
• The E2 action on gec1 gene required the presence of cycloheximide [13].
• Here, we demonstrate that MPP(+) elicited increased autophagy in SH-SY5Y cells, as assessed by electron microscopy, immunofluorescence for the autophagy protein LC3/Atg8, LC3 electrophoretic mobility shift, mitochondrial degradation, and monodansylcadaverine staining for late AVs/autolysosomes [14].
• Atg4 is a novel cysteine protease that processes and deconjugates Atg8 [8].

Physical interactions of GABARAPL1

• Coupled with our previous observation that GEC1 interacts with N-ethylmaleimide-sensitive factor, these findings strongly suggest that GEC1 functions in intracellular trafficking in the biosynthesis pathway and perhaps also the endocytic pathway [12].

Other interactions of GABARAPL1

• GABARAP and gec1/GABARAPL1 genes encode very similar proteins belonging to a new microtubule-associated protein (MAP) family [15].
• Expression of GEC1 greatly increased total and cell-surface KOR but not mu or delta opioid receptors [4].
• Ultrastructural examination of neurons in the paraventricular nucleus of the hypothalamus showed that GEC1 was associated with endoplasmic reticulum and Golgi apparatus and distributed along plasma membranes and in cytosol [12].
• The great majority of the newly synthesized and secreted C3 was found in the glandular epithelial cell incubation [16].

Analytical, diagnostic and therapeutic context of GABARAPL1

• Immunoblotting results showed that GEC1 level was higher in liver and brain than in lung and heart, and very low in kidney and skeletal muscle [12].
• Immunohistochemistry demonstrated that GEC1 immunoreactivity was distributed ubiquitously in the rat CNS with highly intense immunoreactivity in various brain nuclei and motor neurons of the spinal cord [12].
• One of them, called gec1 was then characterized by Northern blot hybridization [13].
• Since secretory component is thought to be a normal glandular epithelial cell product, surgical specimens from patients with mammary carcinoma, an epithelial cancer, were studied with antisera to human free secretory component by indirect immunofluorescence microscopy [17].
• A radioimmunoassay was developed for secretory component, a glandular epithelial cell product secreted as an accessory protein with dimeric immunoglobulins A and M [18].

References