title: Do GGA adaptors bind internal DXXLL motifs?
abstract: The GGA family of clathrin adaptor proteins mediates the intracellular trafficking of transmembrane proteins by interacting with DXXLL-type sorting signals on the latter. These signals were originally identified at the carboxy-termini of the transmembrane cargo proteins. Subsequent studies, however, showed that internal DXXLL sorting motifs occur within the N- or C-terminal cytoplasmic domains of cargo molecules. The GGAs themselves also contain internal DXXLL motifs that serve to auto-regulate GGA function. A recent study challenged the notion that internal DXXLL signals are competent for binding to GGAs. Since the question of whether GGA adaptors interact with internal DXXLL motifs is fundamental to the identification of bona fide GGA cargo, and to an accurate understanding of GGA regulation within cells, we have extended our previous findings. We now present additional evidence confirming that GGAs do interact with internal DXXLL motifs. We also summarize the recent reports from other laboratories documenting internal GGA binding motifs.
authors: Department of Internal Medicine, Washington University School of Medicine, St. Louis, MO 63110, USA.
authors: Balraj
authors: B
authors: Doray
authors: Saurav
authors: S
authors: Misra
authors: Yi
authors: Y
authors: Qian
authors: Tom J
authors: TJ
authors: Brett
authors: Stuart
authors: S
authors: Kornfeld
mesh_terms: D033942:Adaptor Proteins, Vesicular Transport / Q000737:chemistry / Q000378:metabolism*; D020816:Amino Acid Motifs; D000818:Animals; D057809:HEK293 Cells; D006801:Humans; D026503:Low Density Lipoprotein Receptor-Related Protein-1 / Q000737:chemistry / Q000378:metabolism; D051379:Mice; D062105:Molecular Docking Simulation; D011485:Protein Binding; D021382:Protein Sorting Signals; D021381:Protein Transport; D021601:trans-Golgi Network / Q000378:metabolism
chemical_list: D033942:Adaptor Proteins, Vesicular Transport; C407306:GGA adaptor proteins; C483993:LRP12 protein, human; D026503:Low Density Lipoprotein Receptor-Related Protein-1; D021382:Protein Sorting Signals