The study emphasizes the importance of AP2 in the proper functioning of the nervous system, as well as the associations between structural disruptions of the complex and neurodegenerative diseases, highlighting the therapeutic potential arising from the regulation of its subunit expression.
Abstract
This work presents an overall characterization of the endocytosis process, including its various forms, stages, and biological significance. Particular emphasis is placed on clathrin-mediated endocytosis (CME) and the adaptor protein complexes AP1–AP5 that participate in this pathway. Their structure, subcellular localization, function, as well as the disorders and diseases associated with them are addressed. The main attention is devoted to the AP2 complex, which is indispensable in CME. The conformational changes of this complex and their importance in the initiation and progression of clathrin-mediated endocytosis are analysed in detail. The influence of phosphorylation of one of the AP2 subunits on these conformational changes and the positive and negative regulation of the entire AP2 complex by kinases and NECAP proteins is discussed. The study also emphasizes the importance of AP2 in the proper functioning of the nervous system, as well as the associations between structural disruptions of the complex and neurodegenerative diseases, highlighting the therapeutic potential arising from the regulation of its subunit expression.
Adaptor proteins play a critical role in intracellular protein transport by binding to cargoes and facilitating their sorting into vesicles. The adaptor protein 2 (AP2) complex specifically recognizes sorting motifs on cargo proteins such as epidermal growth factor receptor (EGFR) and transferrin receptor (TfR) for pro...
Although the AP-1 clathrin adaptor has been studied for decades, its role in membrane trafficking has been ambiguous. Here, we systematically investigated the localization and function of mammalian AP-1. This adaptor associates with the trans-Golgi network (TGN) and with TGN-related recycling endosomes. Disruption of t...
Fernando M. Valbuena, Maddison Lessard, Adam H. Krahn et al.· bioRxiv· 0 citations
ABSTRACT Clathrin‐mediated endocytosis is a process by which eukaryotic cells internalise a wide range of molecules such as signalling factors, nutrients and membrane proteins, via the formation of a plasma‐membrane‐derived vesicle. This complex mechanism involves a coordinated assembly of the scaffold protein clathrin...
Anne-Laure Boinet, Aurélien Roux, Marko Kaksonen· Traffic : the International...· 0 citations
Potassium channel tetramerization domain-containing protein 17 (KCTD17) is part of the BTB/POZ domain-containing KCTD protein family and serves as a multifunctional regulator of cellular homeostasis. As an adaptor protein associated with Cullin 3 (CUL3)-based E3 ubiquitin ligase complexes, KCTD17 plays a critical role...
The isoform-specific, farnesylated hypervariable region (HVR) of Ras plays an important role in the organization and oligomerization of its globular domain (G-domain) on the surface of the membrane and can control downstream effector binding by positioning the G-domain on the membrane in a specific orientation.
A. Trifan, Hossein Omidi Ardali, J. Vermaas et al.· Membranes· 0 citations
Adaptor protein complex 5 (AP-5) remains the least mechanistically defined member of the mammalian AP family. Recent structural and cell biological studies indicate that it operates within a distinct endolysosomal trafficking machinery together with SPG11 (spatacsin) and SPG15 (spastizin), rather than simply conforming...
Gang Liu, Sun-Rei Yan, Hui-Jing Huang et al.· International Journal of Bio...· 0 citations
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