Abstract
Brain-specific AP180 is present in clathrin coats at equal concentration to the adapter complex, AP2, and assembles clathrin faster than any other protein in vitro. Both AP180 and its ubiquitously expressed homolog clathrin assembly lymphoid myeloid leukemia protein (CALM) control vesicle size and shape in clathrin mediated endocytosis. The clathrin assembly role of AP180 is mediated by a long disordered C-terminal assembly domain. Within this assembly domain, a central acidic clathrin and adapter binding (CLAP) sub-domain contains all of the known short binding motifs for clathrin and AP2. The role of the remaining ∼16 kDa C-terminal sequence has not been clear. We show that this sequence has a separate function in ensuring efficient binding of clathrin, based on in vitro binding and ex vivo transferrin uptake assays. Sequence alignment suggests the C-terminal sub-domain is conserved in CALM.
Highlights
Clathrin mediated endocytosis (CME) occurs in all eukaryotic cells [1]
The adapter protein complex 2 (AP2) in vitro clathrin assembly activities are in doubt because of recent work, which has shown that AP2 is auto-inhibited from recruiting or assembling clathrin until it undergoes a membranemediated conformational change which regulates the availability of a clathrin binding motif (CBM) [18]
Despite that assembly protein 180 (AP180) and clathrin assembly lymphoid myeloid leukemia protein (CALM) are highly abundant components in their respective CME roles, there is no detailed mechanism of AP180 or CALM binding to clathrin, as there is with AP2
Summary
Clathrin mediated endocytosis (CME) occurs in all eukaryotic cells [1]. Multiple endocytic modes occur at presynaptic nerve terminals, but CME is the most well understood [2,3,4,5]. Clathrin is recruited to the membrane by adaptor proteins or protein complexes. The AP2 complex is present in approximately equal concentration with each clathrin triskelion in clathrin coated vesicles. AP2, has a well-defined structure [8,9,10] and functions as an endocytic protein-protein interaction hub [11]. Another adapter, assembly protein 180 (AP180) [12], is present in equal concentration to clathrin triskelia in coated vesicles [13]. AP180 has a ubiquitously expressed homolog, clathrin assembly lymphoid myeloid leukemia protein (CALM), which is abundant as AP2 in clathrin coated vesicles from HeLa cells [14]. Despite that AP180 and CALM are highly abundant components in their respective CME roles, there is no detailed mechanism of AP180 or CALM binding to clathrin, as there is with AP2
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