GABARAP

Case Study 1: Ying Liu, 2021

Few studies have focused on γ-aminobutyric acid type A (GABAA) receptor-associated protein (GABARAP) in tumor progression. The researchers investigated the expression and importance of GABARAP in breast cancer. They analyzed the expression of GABARAP and its relationship with clinicopathological features and prognosis (TCGA). To explain the role and potential mechanism of GABARAP in regulating tumor development, they performed acquisition and loss of function experiments using cell lines and models of mouse xenotransplantation. GABARAP inhibited proliferation, migration and invasion in vitro and in vivo. Notably, low levels of GABARAP induced the epithelial-mesenchymal transition (EMT). Low levels of GABARAP increased p-AKT and p-mTOR levels, and a specific AKT pathway inhibitor reversed the downregulation of GABARAP-induced tumor progression. GABARAP negatively correlated with advanced clinicopathological features in clinical specimens, such as tumor size and TNM stage. Notably, patients with low GABARAP levels had a poor prognosis. Immunohistochemistry (IHC) revealed that GABARAP expression negatively correlated with matrix metalloproteinase (MMP) 2 and MMP14.

Fig1. Western blotting analysis of GABARAP expression in 8 human breast cancer cell lines and non-transformed MCF-10A cells.

Fig2. Correlation analysis of the expression of MMP2 and GABARAP using the Pearson correlation coefficient.

Case Study 2: Shin-ya Kawaguchi, 2007

Fast inhibitory synaptic transmission is predominantly mediated by GABA(A) receptor (GABA(A)R) in the CNS. Although several types of neuronal activity-dependent plasticity at GABAergic synapses have been reported, the detailed mechanism is elusive. Here the researchers show that binding of structurally altered GABA(A)R-associated protein (GABARAP) to GABA(A)R gamma2 subunit and to tubulin is critical for long-term potentiation [called rebound potentiation (RP)] at inhibitory synapses on a cerebellar Purkinje neuron (PN). Either inhibition of GABARAP association with GABA(A)Rgamma2 or deletion of tubulin binding region of GABARAP impaired RP. Thus, precise regulation of GABA(A)Rgamma2-GABARAP-microtubule interaction is critical for RP. Furthermore, competitive inhibition of GABARAP binding to GABA(A)Rgamma2 after the RP establishment attenuated the potentiated response, suggesting that GABARAP is critical not only for the induction but also for the maintenance of RP. Fluorescence resonance energy transfer analysis revealed that GABARAP underwent sustained structural alteration after brief depolarization of a PN depending on the activity of Ca2+/calmodulin-dependent protein kinase II (CaMKII), which is required for the RP induction. The susceptibility of GABARAP to undergo structural alteration was abolished by an amino acid replacement in GABARAP. Furthermore, RP was impaired by expression of the mutant GABARAP with the replacement.

Fig3. Representative traces of mIPSCs before and 30 min after the conditioning depolarization in the presence of control peptide or γ2 peptide.

Fig4. Representative traces and time courses of amplitudes of GABA responses in a PN transfected with either full-length or Δ27 GABARAP.

Fig1. Regulation of GABAA receptor trafficking during SE. (Marco I González, 2011)

Fig2. NPM1/NPM1c bind to GABARAP proteins via an atypical module in their N-terminal regions. (Hannah Mende, 2023)

GABARAP involved in several pathways and played different roles in them. We selected most pathways GABARAP participated on our site, such as Cellular responses to stress, FoxO signaling pathway, GABAergic synapse, which may be useful for your reference. Also, other proteins which involved in the same pathway with GABARAP were listed below. Creative BioMart supplied nearly all the proteins listed, you can search them on our site.

GABARAP has several biochemical functions, for example, GABA receptor binding, beta-tubulin binding, microtubule binding. Some of the functions are cooperated with other proteins, some of the functions could acted by GABARAP itself. We selected most functions GABARAP had, and list some proteins which have the same functions with GABARAP. You can find most of the proteins on our site.

GABARAP has direct interactions with proteins and molecules. Those interactions were detected by several methods such as yeast two hybrid, co-IP, pull-down and so on. We selected proteins and molecules interacted with GABARAP here. Most of them are supplied by our site. Hope this information will be useful for your research of GABARAP.

SQSTM1; CALR; NBR1; ATG7