C-terminal domain of medium Mu1B subunit in epithelial cell-specific clathrin-associated adaptor protein (AP) complex AP-1
AP complexes participate in the formation of intracellular coated transport vesicles and select cargo molecules for incorporation into the coated vesicles in the late secretory and endocytic pathways. There are four AP complexes, AP-1, AP-2, AP-3, and AP-4, described in various eukaryotic organisms. Each AP complex consists of four subunits: two large chains (one each of gamma/alpha/delta/epsilon and beta1-4, respectively), a medium mu chain (mu1-4), and a small sigma chain (sigma1-4). Each of the four subunits from different AP complexes exhibits similarity with each other. This subfamily corresponds to the C-terminal domain of heterotetrameric clathrin-associated adaptor protein complex 1 (AP-1) medium mu1B subunit encoded by ap1m2 gene exclusively expressed in polarized epithelial cells. Epithelial cell-specific AP-1 is used to sort proteins to the basolateral plasma membrane, which involves the formation of clathrin-coated vesicles (CCVs) from the trans-Golgi network (TGN). Recruitment of AP-1 to the TGN membrane is regulated by a small GTPase, ADP-ribosylation factor 1 (ARF1). The phosphorylation/dephosphorylation events can also regulate the function of AP-1. The membrane-anchored cargo molecules can be linked to the outer lattice of CCVs by AP-1. Those cargo molecules interact with adaptors through short sorting signals in their cytosolic segments. Tyrosine-based endocytotic signals are one of the most important sorting signals. They are of the form Y-X-X-Phi, where Y is tyrosine, X is any amino acid and Phi is a bulky hydrophobic residue that can be Leu, Ile, Met, Phe, or Val. These kinds of sorting signals can be recognized by the C-terminal domain of AP-1 mu1B subunit, also known as Y-X-X-Phi signal-binding domain that contains two hydrophobic pockets, one for the tyrosine-binding and one for the bulky hydrophobic reside-binding. Besides, AP-1 mu1B subunit mediates the basolateral recycling of low-density lipoprotein receptor (LDLR) and transferrin receptor (TfR) from the sorting endosomes, where the basolateral sorting signal does not belong to the tyrosine-based signals. Thus, the binding site in mu1B subunit of AP-1 for the signals of LDLR and TfR might be distinct from that for YXXPhi signals.
Comment:Based on structure that shows that mouse mu1 adaptin subunit of AP-2 adaptor binds signal peptides.
Comment:C-terminal domain of heterotetrameric adaptor protein (AP) complexes medium mu subunits binds Y-X-X-Phi-type tyrosine-based signals, where Y is tyrosine, X is any amino acid and Phi is a bulky hydrophobic residue that can be Leu, Ile, Met, Phe, or Val.
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