Open AccessHuntingtin-associated protein 1 regulates inhibitory synaptic transmission by modulating γ-aminobutyric acid type A receptor membrane trafficking
Author(s) -
Josef T. Kittler,
Philip Thomas,
Verena Tretter,
Yury Bogdanov,
Volker Haucke,
Trevor G. Smart,
Stephen J. Moss
Publication year - 2004
Publication title -
proceedings of the national academy of sciences of the united states of america
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.011
H-Index - 771
eISSN - 1091-6490
pISSN - 0027-8424
DOI - 10.1073/pnas.0401860101
Subject(s) - endocytic cycle , huntingtin , endocytosis , inhibitory postsynaptic potential , microbiology and biotechnology , neurotransmission , receptor , biology , gaba receptor , gamma aminobutyric acid , gabaa receptor , biochemistry , neuroscience , mutant , gene
Gamma-aminobutyric acid type A receptors (GABA(A)Rs) are the major sites of fast synaptic inhibition in the brain. An essential determinant for the efficacy of synaptic inhibition is the regulation of GABA(A)R cell surface stability. Here, we have examined the regulation of GABA(A)R endocytic sorting, a critical regulator of cell surface receptor number. In neurons, rapid constitutive endocytosis of GABA(A)Rs was evident. Internalized receptors were then either rapidly recycled back to the cell surface, or on a slower time scale, targeted for lysosomal degradation. This sorting decision was regulated by a direct interaction of GABA(A)Rs with Huntingtin-associated protein 1 (HAP1). HAP1 modulated synaptic GABA(A)R number by inhibiting receptor degradation and facilitating receptor recycling. Together these observations have identified a role for HAP1 in regulating GABA(A)R sorting, suggesting an important role for this protein in the construction and maintenance of inhibitory synapses.