Regulation of GABA(A)-receptor surface expression with special reference to the involvement of GABARAP (GABA(A) receptor-associated protein) and PRIP (phospholipase C-related, but catalytically inactive protein).
GABA(A) receptors are heteropentameric ligand-gated chloride channels composed of a variety of subunits, including alpha1 - 6, beta1 - 3, gamma1 - 3, delta, epsilon, theta, and pi, and play a key role in controlling inhibitory neuronal activity. Modification of the efficacy of the synaptic strength is produced by changes in both the number of neuronal surface receptors and pentameric molecular assembly, leading to differences of sensitivity to neurotransmitters and neuromimetic drugs. Therefore, it is important to understand the molecular mechanisms regulating the so-called "life cycle of GABA(A) receptors" including sequential pentameric assembly at the site synthesized, intracellular transport through the Golgi apparatus and the cytoplasm, insertion into the cell membrane, functional modulation at the cell surface, and finally internalization, followed by either recycling back to the surface membrane or lysosomal degradation. This review is focused on events related to the surface expression of the receptor containing the gamma2 subunit and clathrin/AP2 complex-mediated phospho-regulated endocytosis of the receptor, with special reference to the function of novel GABA(A) receptor modulators, GABARAP (GABA(A) receptor-associated protein) and PRIP (phospholipase C-related, but catalytically inactive protein).
Kanematsu
Takashi
T
Laboratory of Molecular and Cellular Biochemistry, Faculty of Dental Science and Station for Collaborative Research, Kyushu University, Fukuoka, Japan. inositol@dent.kyushu-u.ac.jp
Mizokami
Akiko
A
Watanabe
Keiko
K
Hirata
Masato
M
D033962:Adaptor Protein Complex 2 / Q000378:metabolism; D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism*; D051017:Apoptosis Regulatory Proteins; D002966:Clathrin / Q000378:metabolism; D004705:Endocytosis / Q000502:physiology; D005786:Gene Expression Regulation; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism*; D008869:Microtubule-Associated Proteins / Q000378:metabolism*; D056918:Nuclear Receptor Coactivators; D011963:Receptors, GABA-A / Q000378:metabolism*
D033962:Adaptor Protein Complex 2; D048868:Adaptor Proteins, Signal Transducing; D051017:Apoptosis Regulatory Proteins; D002966:Clathrin; C116741:GABARAP protein, human; C546279:GABRG2 protein, human; D047908:Intracellular Signaling Peptides and Proteins; D008869:Microtubule-Associated Proteins; C486559:NCOA6 protein, human; D056918:Nuclear Receptor Coactivators; D011963:Receptors, GABA-A