An ear-core interaction regulates the recruitment of the AP-3 complex to membranes.
AP-3 is a heterotetrameric adaptor involved in the biogenesis of lysosome-related organelles. The function of AP-3 as an adaptor relies on its ability to bind to membranes in an Arf-dependent fashion and to recognize sorting signals in the cytosolic tails of the transmembrane cargo. Here, we report an interdomain interaction involving the ear domain of the delta subunit and the sigma3 subunit of AP-3. This interaction interferes with the binding of AP-3 to Arf but not to dileucine-based sorting signals. As a consequence, the delta-ear inhibits the recruitment of AP-3 to membranes both in vitro and in vivo and impairs the sorting of lysosomal membrane proteins. These observations suggest a new regulatory mechanism for the recruitment of AP-3 to membranes involving delta-ear-sigma3 interactions.
Cell Biology and Metabolism Branch, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892, USA.
Stephane
S
Lefrançois
Katy
K
Janvier
Markus
M
Boehm
Chean Eng
CE
Ooi
Juan S
JS
Bonifacino
D033963:Adaptor Protein Complex 3; D033966:Adaptor Protein Complex beta Subunits; D000595:Amino Acid Sequence; D019943:Amino Acid Substitution; D000818:Animals; D019556:COS Cells; D002457:Cell Extracts; D002522:Chlorocebus aethiops; D002999:Clone Cells; D011992:Endosomes / Q000737:chemistry; D005434:Flow Cytometry; D005982:Glutathione Transferase / Q000378:metabolism; D006367:HeLa Cells; D006801:Humans; D008566:Membranes / Q000378:metabolism*; D008954:Models, Biological; D011487:Protein Conformation; D017434:Protein Structure, Tertiary / Q000502:physiology*; D021122:Protein Subunits / Q000737:chemistry* / Q000378:metabolism; D021381:Protein Transport; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D014157:Transcription Factors / Q000037:antagonists & inhibitors* / Q000737:chemistry; D020798:Two-Hybrid System Techniques
D033963:Adaptor Protein Complex 3; D033966:Adaptor Protein Complex beta Subunits; C113910:Ap3d1 protein, mouse; D002457:Cell Extracts; D021122:Protein Subunits; D011993:Recombinant Fusion Proteins; D014157:Transcription Factors; D005982:Glutathione Transferase