Topic
AP2 adaptor complex
About: AP2 adaptor complex is a research topic. Over the lifetime, 16 publications have been published within this topic receiving 1738 citations. The topic is also known as: AP-2 Complex.
Papers
TL;DR: In this article, a previously uncharacterized atypical clathrin adaptor protein 2 (AP2) binding motif (KTHLRRRSSQLK in the β3 subunit) was identified within the intracellular domains of all GABA A R β subunit isoforms.
Abstract: The efficacy of synaptic inhibition depends on the number of γ-aminobutyric acid type A receptors (GABA A Rs) expressed on the cell surface of neurons. The clathrin adaptor protein 2 (AP2) complex is a critical regulator of GABA A R endocytosis and, hence, surface receptor number. Here, we identify a previously uncharacterized atypical AP2 binding motif conserved within the intracellular domains of all GABA A R β subunit isoforms. This AP2 binding motif (KTHLRRRSSQLK in the β3 subunit) incorporates the major sites of serine phosphorylation within receptor β subunits, and phosphorylation within this site inhibits AP2 binding. Furthermore, by using surface plasmon resonance, we establish that a peptide (pepβ3) corresponding to the AP2 binding motif in the GABA A R β3 subunit binds to AP2 with high affinity only when dephosphorylated. Moreover, the pepβ3 peptide, but not its phosphorylated equivalent (pepβ3-phos), enhanced the amplitude of miniature inhibitory synaptic current and whole cell GABA A R current. These effects of pepβ3 on GABA A R current were occluded by inhibitors of dynamin-dependent endocytosis supporting an action of pepβ3 on GABA A R endocytosis. Therefore phospho-dependent regulation of AP2 binding to GABA A Rs provides a mechanism to specify receptor cell surface number and the efficacy of inhibitory synaptic transmission.
202 citations
TL;DR: It is shown that two independent C‐terminal signals determine AQP4 basolateral membrane targeting in epithelial MDCK cells, and stress‐induced kinase casein kinase (CK)II phosphorylates the Ser276 immediately preceding the tyrosine motif, increasing AQp4–μ3A interaction and enhancing AQP 4–lysosomal targeting and degradation.
Abstract: Aquaporin 4 (AQP4) is the predominant water channel in the brain. It is targeted to specific membrane domains of astrocytes and plays a crucial role in cerebral water balance in response to brain edema formation. AQP4 is also specifically expressed in the basolateral membranes of epithelial cells. However, the molecular mechanisms involved in its polarized targeting and membrane trafficking remain largely unknown. Here, we show that two independent C-terminal signals determine AQP4 basolateral membrane targeting in epithelial MDCK cells. One signal involves a tyrosine-based motif; the other is encoded by a di-leucine-like motif. We found that the tyrosine-based basolateral sorting signal also determines AQP4 clathrin-dependent endocytosis through direct interaction with the mu subunit of AP2 adaptor complex. Once endocytosed, a regulated switch in mu subunit interaction changes AP2 adaptor association to AP3. We found that the stress-induced kinase casein kinase (CK)II phosphorylates the Ser276 immediately preceding the tyrosine motif, increasing AQP4-mu 3A interaction and enhancing AQP4-lysosomal targeting and degradation. AQP4 phosphorylation by CKII may thus provide a mechanism that regulates AQP4 cell surface expression.
166 citations
TL;DR: It is shown that phosphorylation of a single threonine residue (Thr156) of the mu2 subunit of the AP2 complex is essential for efficient endocytosis of transferrin both in an in vitro coated-pit budding assay and in living cells.
144 citations
TL;DR: Electron cryomicroscopy of the clathrin coat and X-ray crystallography of parts of theclathrin heavy chain combine to give a detailed picture of theClathrin molecule, assembled as a cage.
125 citations
TL;DR: The data suggest that not only Tyr-333 but also its context is important in determining the specificity of binding of TGN38 to μ2, which is in contrast to previously published work.
46 citations
Related Topics (5)
Performance Metrics
| Year | Papers |
|---|---|
| 2021 | 2 |
| 2018 | 1 |
| 2010 | 1 |
| 2008 | 1 |
| 2005 | 3 |
| 2002 | 1 |