GABARAP: lessons for synaptogenesis.
The clustering of neurotransmitter receptors at the postsynaptic terminals is a critical requirement for efficient neurotransmission and neuronal communication. This process is facilitated by adaptor proteins, which bridge the postsynaptic receptors and the underlying cytoskeleton. One such molecule, the GABAA receptor-associated protein, GABARAP, was identified as a potential linker between GABAA receptors and microtubules. GABARAP belongs to an expanding family of proteins that are implicated in a variety of intracellular transport processes. GABARAP has been shown to interact with myriad binding partners, including the gamma2 subunit of the GABAA receptor, tubulin and microtubules, the N-ethyl maleimide sensitive factor, gephyrin, and the transferin receptor. The recent determination of the GABARAP crystal structure has revealed individual GABARAP domains, motifs, and surface regions involved in specific protein-protein interactions. Currently, a more general role is emerging for GABARAP, including shipping GABAA receptors to and from the cell surface, organizing them into postsynaptic clusters, and regulating the steady-state receptor density.
Coyle
Joseph E
JE
Cellular Biochemistry and Biophysics Program, Memorial Sloan-Kettering Cancer Center, New York, NY 10021, USA.
Nikolov
Dimitar B
DB
D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D051017:Apoptosis Regulatory Proteins; D003599:Cytoskeleton / Q000502:physiology; D006801:Humans; D008869:Microtubule-Associated Proteins / Q000737:chemistry / Q000145:classification / Q000235:genetics / Q000502:physiology*; D008958:Models, Molecular; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D021381:Protein Transport / Q000502:physiology; D011963:Receptors, GABA-A / Q000737:chemistry / Q000235:genetics / Q000502:physiology*; D018009:Receptors, Glycine / Q000502:physiology; D013569:Synapses / Q000502:physiology*
D048868:Adaptor Proteins, Signal Transducing; D051017:Apoptosis Regulatory Proteins; C116741:GABARAP protein, human; D008869:Microtubule-Associated Proteins; D011963:Receptors, GABA-A; D018009:Receptors, Glycine