6oxl

Structural highlights

Function

[AP2S1_RAT] Component of the adaptor protein complex 2 (AP-2). Adaptor protein complexes function in protein Transport via Transport vesicles in different membrane traffic pathways. Adaptor protein complexes are vesicle coat components and appear to be involved in cargo selection and vesicle formation. AP-2 is involved in clathrin-dependent endocytosis in which cargo proteins are incorporated into vesicles surrounded by clathrin (clathrin-coated vesicles, CCVs) which are destined for fusion with the early endosome. The clathrin lattice serves as a mechanical scaffold but is itself unable to bind directly to membrane components. Clathrin-associated adaptor protein (AP) complexes which can bind directly to both the clathrin lattice and to the lipid and protein components of membranes are considered to be the major clathrin adaptors contributing the CCV formation. AP-2 also serves as a cargo receptor to selectively sort the membrane proteins involved in receptor-mediated endocytosis. AP-2 seems to play a role in the recycling of synaptic vesicle membranes from the presynaptic surface. AP-2 recognizes Y-X-X-[FILMV] (Y-X-X-Phi) and [ED]-X-X-X-L-[LI] endocytosis signal motifs within the cytosolic tails of transmembrane cargo molecules. AP-2 may also play a role in maintaining normal post-endocytic trafficking through the ARF6-regulated, non-clathrin pathway. The AP-2 alpha and AP-2 sigma subunits are thought to contribute to the recognition of the [ED]-X-X-X-L-[LI] motif. May also play a role in extracellular calcium homeostasis (By similarity).^{[1] [2]} [AP2M1_MOUSE] Component of the adaptor protein complex 2 (AP-2). Adaptor protein complexes function in protein transport via transport vesicles in different membrane traffic pathways. Adaptor protein complexes are vesicle coat components and appear to be involved in cargo selection and vesicle formation. AP-2 is involved in clathrin-dependent endocytosis in which cargo proteins are incorporated into vesicles surrounded by clathrin (clathrin-coated vesicles, CCVs) which are destined for fusion with the early endosome. The clathrin lattice serves as a mechanical scaffold but is itself unable to bind directly to membrane components. Clathrin-associated adaptor protein (AP) complexes which can bind directly to both the clathrin lattice and to the lipid and protein components of membranes are considered to be the major clathrin adaptors contributing the CCV formation. AP-2 also serves as a cargo receptor to selectively sort the membrane proteins involved in receptor-mediated endocytosis. AP-2 seems to play a role in the recycling of synaptic vesicle membranes from the presynaptic surface. AP-2 recognizes Y-X-X-[FILMV] (Y-X-X-Phi) and [ED]-X-X-X-L-[LI] endocytosis signal motifs within the cytosolic tails of transmembrane cargo molecules. AP-2 may also play a role in maintaining normal post-endocytic trafficking through the ARF6-regulated, non-clathrin pathway. During long-term potentiation in hippocampal neurons, AP-2 is responsible for the endocytosis of ADAM10 (PubMed:23676497). The AP-2 mu subunit binds to transmembrane cargo proteins; it recognizes the Y-X-X-Phi motifs. The surface region interacting with to the Y-X-X-Phi motif is inaccessible in cytosolic AP-2, but becomes accessible through a conformational change following phosphorylation of AP-2 mu subunit at 'Tyr-156' in membrane-associated AP-2. The membrane-specific phosphorylation event appears to involve assembled clathrin which activates the AP-2 mu kinase AAK1 (By similarity). Plays a role in endocytosis of frizzled family members upon Wnt signaling (By similarity).^{[3] [4] [5]} [AP2B1_MOUSE] Component of the adaptor protein complex 2 (AP-2). Adaptor protein complexes function in protein transport via transport vesicles in different membrane traffic pathways. Adaptor protein complexes are vesicle coat components and appear to be involved in cargo selection and vesicle formation. AP-2 is involved in clathrin-dependent endocytosis in which cargo proteins are incorporated into vesicles surrounded by clathrin (clathrin-coated vesicles, CCVs) which are destined for fusion with the early endosome. The clathrin lattice serves as a mechanical scaffold but is itself unable to bind directly to membrane components. Clathrin-associated adaptor protein (AP) complexes which can bind directly to both the clathrin lattice and to the lipid and protein components of membranes are considered to be the major clathrin adaptors contributing the CCV formation. AP-2 also serves as a cargo receptor to selectively sort the membrane proteins involved in receptor-mediated endocytosis. AP-2 seems to play a role in the recycling of synaptic vesicle membranes from the presynaptic surface. AP-2 recognizes Y-X-X-[FILMV] (Y-X-X-Phi) and [ED]-X-X-X-L-[LI] endocytosis signal motifs within the cytosolic tails of transmembrane cargo molecules. AP-2 may also play a role in maintaining normal post-endocytic trafficking through the ARF6-regulated, non-clathrin pathway. During long-term potentiation in hippocampal neurons, AP-2 is responsible for the endocytosis of ADAM10 (PubMed:23676497). The AP-2 beta subunit acts via its C-terminal appendage domain as a scaffolding platform for endocytic accessory proteins; at least some clathrin-associated sorting proteins (CLASPs) are recognized by their [DE]-X(1,2)-F-X-X-[FL]-X-X-X-R motif. The AP-2 beta subunit binds to clathrin heavy chain, promoting clathrin lattice assembly; clathrin displaces at least some CLASPs from AP2B1 which probably then can be positioned for further coat assembly (By similarity).^{[6] [7] [8]} [NECP2_MOUSE] Involved in endocytosis.

References

1. ↑ Nakatsu F, Ohno H. Adaptor protein complexes as the key regulators of protein sorting in the post-Golgi network. Cell Struct Funct. 2003 Oct;28(5):419-29. PMID:14745134
2. ↑ Owen DJ, Collins BM, Evans PR. Adaptors for clathrin coats: structure and function. Annu Rev Cell Dev Biol. 2004;20:153-91. PMID:15473838 doi:10.1146/annurev.cellbio.20.010403.104543
3. ↑ Nakatsu F, Ohno H. Adaptor protein complexes as the key regulators of protein sorting in the post-Golgi network. Cell Struct Funct. 2003 Oct;28(5):419-29. PMID:14745134
4. ↑ Owen DJ, Collins BM, Evans PR. Adaptors for clathrin coats: structure and function. Annu Rev Cell Dev Biol. 2004;20:153-91. PMID:15473838 doi:10.1146/annurev.cellbio.20.010403.104543
5. ↑ Marcello E, Saraceno C, Musardo S, Vara H, de la Fuente AG, Pelucchi S, Di Marino D, Borroni B, Tramontano A, Perez-Otano I, Padovani A, Giustetto M, Gardoni F, Di Luca M. Endocytosis of synaptic ADAM10 in neuronal plasticity and Alzheimer's disease. J Clin Invest. 2013 Jun;123(6):2523-38. doi: 10.1172/JCI65401. Epub 2013 May 8. PMID:23676497 doi:http://dx.doi.org/10.1172/JCI65401
6. ↑ Nakatsu F, Ohno H. Adaptor protein complexes as the key regulators of protein sorting in the post-Golgi network. Cell Struct Funct. 2003 Oct;28(5):419-29. PMID:14745134
7. ↑ Owen DJ, Collins BM, Evans PR. Adaptors for clathrin coats: structure and function. Annu Rev Cell Dev Biol. 2004;20:153-91. PMID:15473838 doi:10.1146/annurev.cellbio.20.010403.104543
8. ↑ Marcello E, Saraceno C, Musardo S, Vara H, de la Fuente AG, Pelucchi S, Di Marino D, Borroni B, Tramontano A, Perez-Otano I, Padovani A, Giustetto M, Gardoni F, Di Luca M. Endocytosis of synaptic ADAM10 in neuronal plasticity and Alzheimer's disease. J Clin Invest. 2013 Jun;123(6):2523-38. doi: 10.1172/JCI65401. Epub 2013 May 8. PMID:23676497 doi:http://dx.doi.org/10.1172/JCI65401
9. ↑ Partlow EA, Baker RW, Beacham GM, Chappie JS, Leschziner AE, Hollopeter G. A structural mechanism for phosphorylation-dependent inactivation of the AP2 complex. Elife. 2019 Aug 29;8. pii: 50003. doi: 10.7554/eLife.50003. PMID:31464684 doi:http://dx.doi.org/10.7554/eLife.50003