期刊
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
卷 101, 期 34, 页码 12736-12741出版社
NATL ACAD SCIENCES
DOI: 10.1073/pnas.0401860101
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资金
- Medical Research Council [G9603438] Funding Source: Medline
- Medical Research Council [G9603438] Funding Source: researchfish
- MRC [G9603438] Funding Source: UKRI
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 GABAAR sorting, suggesting an important role for this protein in the construction and maintenance of inhibitory synapses.
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