Gamma-aminobutyric acid receptor-associated protein

Definition:

Ubiquitin-like modifier that plays a role in intracellular transport of GABA(A) receptors and its interaction with the cytoskeleton. Involved in autophagy: while LC3s are involved in elongation of the phagophore membrane, the GABARAP/GATE-16 subfamily is essential for a later stage in autophagosome maturation. Through its interaction with the reticulophagy receptor TEX264, participates in the remodeling of subdomains of the endoplasmic reticulum into autophagosomes upon nutrient stress, which then fuse with lysosomes for endoplasmic reticulum turnover. Also required for the local activation of the CUL3(KBTBD6/7) E3 ubiquitin ligase complex, regulating ubiquitination and degradation of TIAM1, a guanyl-nucleotide exchange factor (GEF) that activates RAC1 and downstream signal transduction. Thereby, regulates different biological processes including the organization of the cytoskeleton, cell migration and proliferation. Involved in apoptosis.

References:

[1]. Christian Behrends, et al. Network organization of the human autophagy system. Nature. 2010 Jul 1;466(7302):68-76. [Content Brief]

[2]. Haruka Chino, et al. Intrinsically Disordered Protein TEX264 Mediates ER-phagy. Mol Cell. 2019 Jun 6;74(5):909-921.e6. [Content Brief]

[3]. H Wang, et al. GABA(A)-receptor-associated protein links GABA(A) receptors and the cytoskeleton. Nature. 1999 Jan 7;397(6714):69-72. [Content Brief]

[4]. David Colecchia, et al. MAPK15/ERK8 stimulates autophagy by interacting with LC3 and GABARAP proteins. Autophagy. 2012 Dec;8(12):1724-40. [Content Brief]

[5]. Yukiko Kabeya, et al. LC3, GABARAP and GATE16 localize to autophagosomal membrane depending on form-II formation. J Cell Sci. 2004 Jun 1;117(Pt 13):2805-12. [Content Brief]

[6]. Heide Marika Genau, et al. CUL3-KBTBD6/KBTBD7 ubiquitin ligase cooperates with GABARAP proteins to spatially restrict TIAM1-RAC1 signaling. Mol Cell. 2015 Mar 19;57(6):995-1010. [Content Brief]

[7]. Jeong Heon Lee, et al. GABAA receptor-associated protein (GABARAP) induces apoptosis by interacting with DEAD (Asp-Glu-Ala-Asp/His) box polypeptide 47 (DDX 47). Biotechnol Lett. 2005 May;27(9):623-8. [Content Brief]

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