Identification of the universal cofactor (auxilin 2) in clathrin coat dissociation

Molecular Structure, Function, and Dynamics of Clathrin-Mediated Membrane Traffic

“…Clathrin-coated vesicles from this recycling process that have been isolated from mammalian brain are the principal source of material for most biochemical and structural analyses. The presence of brain-specific isoforms of clathrin light chains (Jackson et al 1987;Kirchhausen et al 1987), auxilin (Umeda et al 2000), dynamin (Urrutia et al 1997), AP180 (Bushlin et al 2008), and various other proteins of the presynaptic membrane-recycling pathway may reflect features of the clathrin cycle in synapses that are not shared with classical, receptor-mediated endocytosis as studied in epithelial cells and fibroblasts.…”

“…The J-domain, in turn, recruits and activates the uncoating ATPase Hsc70, as described in the section on coated vesicle dynamics below. There are two auxilin isoforms in vertebrates: the brain-specific auxilin 1 and the ubiquitous auxilin 2 or GAK (Ungewickell et al 1995;Umeda et al 2000). The J-domain is at the carboxyl terminus of both, preceded by a clathrin-binding segment.…”

Direct interaction of Cbl with pTyr 1045 of the EGF receptor (EGFR) is required to sort the EGFR to lysosomes for degradation

“…Binding of 2 to tyrosine-based sorting signals is proposed to be dependent upon phosphorylation of 2, likely mediated by the kinases AAK1 (Adaptor-Associated Kinase 1) and GAK (cyclin-G-Associated protein Kinase) (Umeda et al, 2000;Olusanya et al, 2001;Collins et al, 2002;Conner and Schmid, 2002;Korolchuk and Banting, 2002;Ricotta et al, 2002;Sorkin, 2004). Other receptors are believed to make use of additional connector proteins coupling their sorting signals to the clathrin coat.…”

Endocytic Accessory Factors and Regulation of Clathrin-Mediated Endocytosis

“…Following scission, CCVs rapidly shed their clathrin coat through the coordinated action of the ATPase/chaperone Hsc70 (Chappell et al 1986) and neuronal J-domain kinase (Ahle and Ungewickell 1990) or ubiquitous paralog auxilin2 (cyclin-G-associated kinase, GAK) (Greener et al 2000;Umeda et al 2000).…”