TY - JOUR
T1 - Clathrin- and AP-2-binding Sites in HIP1 Uncover a General Assembly Role for Endocytic Accessory Proteins
AU - Mishra, Sanjay K.
AU - Agostinelli, Nicole R.
AU - Brett, Tom J.
AU - Mizukami, Ikuko
AU - Ross, Theodora S.
AU - Traub, Linton M.
PY - 2001/12/7
Y1 - 2001/12/7
N2 - Clathrin-mediated endocytosis is a major pathway for the internalization of macromolecules into the cytoplasm of eukaryotic cells. The principle coat components, clathrin and the AP-2 adaptor complex, assemble a polyhedral lattice at plasma membrane bud sites with the aid of several endocytic accessory proteins. Here, we show that huntingtin-interacting protein 1 (HIP1), a binding partner of huntingtin, copurifies with brain clathrin-coated vesicles and associates directly with both AP.2 and clathrin. The discrete interaction sequences within HIP1 that facilitate binding are analogous to motifs present in other accessory proteins, including AP180, amphiphysin, and epsin. Bound to a phosphoinositide-containing membrane surface via an epsin N-terminal homology (ENTH) domain, HIP1 associates with AP-2 to provide coincident clathrin-binding sites that together efficiently recruit clathrin to the bilayer. Our data implicate HIP1 in endocytosis, and the similar modular architecture and function of HIP1, epsin, and AP180 suggest a common role in lipid-regulated clathrin lattice biogenesis.
AB - Clathrin-mediated endocytosis is a major pathway for the internalization of macromolecules into the cytoplasm of eukaryotic cells. The principle coat components, clathrin and the AP-2 adaptor complex, assemble a polyhedral lattice at plasma membrane bud sites with the aid of several endocytic accessory proteins. Here, we show that huntingtin-interacting protein 1 (HIP1), a binding partner of huntingtin, copurifies with brain clathrin-coated vesicles and associates directly with both AP.2 and clathrin. The discrete interaction sequences within HIP1 that facilitate binding are analogous to motifs present in other accessory proteins, including AP180, amphiphysin, and epsin. Bound to a phosphoinositide-containing membrane surface via an epsin N-terminal homology (ENTH) domain, HIP1 associates with AP-2 to provide coincident clathrin-binding sites that together efficiently recruit clathrin to the bilayer. Our data implicate HIP1 in endocytosis, and the similar modular architecture and function of HIP1, epsin, and AP180 suggest a common role in lipid-regulated clathrin lattice biogenesis.
UR - http://www.scopus.com/inward/record.url?scp=0035824673&partnerID=8YFLogxK
U2 - 10.1074/jbc.M108177200
DO - 10.1074/jbc.M108177200
M3 - Article
C2 - 11577110
AN - SCOPUS:0035824673
SN - 0021-9258
VL - 276
SP - 46230
EP - 46236
JO - Journal of Biological Chemistry
JF - Journal of Biological Chemistry
IS - 49
ER -