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Sorting of Mannose 6-Phosphate Receptors Mediated by the GGAs

Science  01 Jun 2001:
Vol. 292, Issue 5522, pp. 1712-1716
DOI: 10.1126/science.1060750

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Abstract

The delivery of soluble hydrolases to lysosomes is mediated by the cation-independent and cation-dependent mannose 6-phosphate receptors. The cytosolic tails of both receptors contain acidic-cluster-dileucine signals that direct sorting from the trans-Golgi network to the endosomal-lysosomal system. We found that these signals bind to the VHS domain of the Golgi-localized, γ-ear–containing, ARF-binding proteins (GGAs). The receptors and the GGAs left the trans-Golgi network on the same tubulo-vesicular carriers. A dominant-negative GGA mutant blocked exit of the receptors from the trans-Golgi network. Thus, the GGAs appear to mediate sorting of the mannose 6-phosphate receptors at the trans-Golgi network.

  • * These authors contributed equally to this work.

  • To whom correspondence should be addressed. E-mail: juan{at}helix.nih.gov

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