The 46-kDa Mannose 6-Phosphate Receptor Contains Multiple Binding Sites for Clathrin Adaptors*

HOENING S; MIGUEL A. SOSA; VON FIGURA K; MALCHIODI EL

JOURNAL OF BIOLOGICAL CHEMISTRY (ONLINE)

American Society for Biochemistry and Molecular Biology

Año: 1997 vol. 272 p. 19884 - 19890

1083-351X

The two known mannose 6-phosphate receptors(MPR46 and MPR300) both mediate the transport ofMan-6-P-containing lysosomal proteins to lysosomes.However, the MPRs cannot be detected in lysosomes,instead they recycle between the plasma membrane andendosomes and between endosomes and the trans-Golginetwork. Both, endocytosis from the plasma membraneand budding of transport vesicles from the trans-Golginetwork involves the interaction of the receptor withthe clathrin-coated vesicles-associated protein complexesAP1 and AP2. We have analyzed this interactionbetween the Golgi-restricted AP1 complex and theplasma membrane-restricted AP2 complex with theMPR46 tail in vitro by using a biosensor.AP1 and AP2 both bind to and dissociate from theMPR46 tail with similar kinetics. Using synthetic peptidescorresponding to different MPR receptor tail regionsin inhibition and binding studies, a common highaffinity binding site for AP1 and AP2 and two separatehigh affinity binding sites for AP1 and AP2, respectively,were identified.