LIG_AP_GAE_1

Clathrin coated vesicles (CCV) are components of endocytosis and trafficking between the Trans Golgi Network (TGN) and endosomes. During CCV formation (less well characterized for internal membranes than for endocytosis), clathrin and clathrin adaptors interact to nucleate coat assembly by binding to appropriate membranes and recruit cargo molecules, clathrin and other coat associated proteins. The clathrin adaptors implicated in CCV formation at the TGN and endosomes are AP-1 and Ggas. AP-1 heterotetrameric complex contains a gamma-adaptin subunit bearing a gamma-ear at its carboxy terminus, while Ggas are monomeric adaptor proteins containing a C-terminal domain related to the ear domain of gamma-adaptin. By analogy with AP-2 (the well characterized adaptor complex involved in endocytic CCV formation) the gamma-ear domain of AP-1 and Ggas probably mediate interactions with accessory proteins during CCV formation.
A novel conserved motif (Acidic Phenylalanine motif) has been described on 2 functionally related Epsin-related proteins (Ent3p and Ent5p) in yeast (S.cerevisiae) . It mediates the interaction between the 2 proteins Ent3p and Ent5p and the gamma-ear domains of Gga2p and AP-1. Ent3p and Ent5p cooperate with Ggas and AP-1 to recruit clathrin and promote the formation of clathrin coats at the Golgi/endosomes (Duncan,2003). A specific role in clathrin localization and assembly on TGN/endosome membranes and in traffic between the TGN and endosomes has been proposed for this motif. The motif is also found in vacuole sorting proteins in yeast (Vps3p and Vps72p), in ENTH containing (uncharacterized) S.pombe and C.elegans proteins, in gamma-synergin and in Rabaptin 5 (human, mouse and rat). Recently, new GAE partners have been identified by combinatorial phage display and in vitro binding studies (Mattera,2004, Lui,2003).