TY - JOUR
T1 - The mannose 6-phosphate receptor and the biogenesis of lysosomes
AU - Griffiths, Gareth
AU - Hoflack, Bernard
AU - Simons, Kai
AU - Mellman, Ira
AU - Kornfeld, Stuart
N1 - Funding Information:
This paper is dedicated to the memory of Dr. Alex B. Novikoff, Many thanks are due to Ruth Back, Michael Hollinshead, and Hilkka Virta (EMBL) for excellent technical assistance and to Raffaele Matteoni, who provided cultures of NRK cells. The DAMP reagent and the anti-DNP antibodies were a kind gift of Dr. Richard Anderson, and the a~macrogiobulin was generously provided by Dr. Fred Maxfield. We are also grateful to Dr. Robin Andy and Dr. David Sabatini for providing the affinity-purified anti-13 glucuronidase antibody, and to Dr. Walter Gregory for the gift of the anti-cathepsin D serum. Finally, we thank Drs. Bo van Deurs, Klaus-Peter Zimmer, and Sandra Schmid for critically reading the manuscript, and Rachel Wainwright for typing it. This work was supported in part by United States Public Service Grant RO1 CA 08759 (to S. Kornfeld) and RO1 GM 27965 (to I. Mellman). The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 16 U.S.C. Section 1734 solely to indicate this fact.
PY - 1988/2/12
Y1 - 1988/2/12
N2 - Localization of the 215 kd mannose 6-phosphate receptor(MPR) was studied in normal rat kidney cells. Low levels of receptor were detected in the trans Golgi network, Golgi stack, plasma membrane, and peripheral endosomes. The bulk of the receptor was localized to an acidic, reticular-vesicular structure adjacent to the Golgi complex. The structure also labeled with antibodies to lysosomal enzymes and a lysosomal membrane glycoprotein (Igp120). While lysosome-like, this structure is not a typical lysosome that is devoid of MPRs. The endocytic marker α2macroglobulin-gold entered the structure at 37°C, but not at 20°C. With prolonged chase, most of the marker was transported from the structure into lysosomes. We propose that the MPR/Igp-enriched structure is a specialized endosome (prelysosome) that serves as an intermediate compartment into which endocytic vesicles discharge their contents, and where lysosomal enzymes are released from the MPR and packaged along with newly synthesized lysosomal glycoproteins into lysosomes.
AB - Localization of the 215 kd mannose 6-phosphate receptor(MPR) was studied in normal rat kidney cells. Low levels of receptor were detected in the trans Golgi network, Golgi stack, plasma membrane, and peripheral endosomes. The bulk of the receptor was localized to an acidic, reticular-vesicular structure adjacent to the Golgi complex. The structure also labeled with antibodies to lysosomal enzymes and a lysosomal membrane glycoprotein (Igp120). While lysosome-like, this structure is not a typical lysosome that is devoid of MPRs. The endocytic marker α2macroglobulin-gold entered the structure at 37°C, but not at 20°C. With prolonged chase, most of the marker was transported from the structure into lysosomes. We propose that the MPR/Igp-enriched structure is a specialized endosome (prelysosome) that serves as an intermediate compartment into which endocytic vesicles discharge their contents, and where lysosomal enzymes are released from the MPR and packaged along with newly synthesized lysosomal glycoproteins into lysosomes.
UR - http://www.scopus.com/inward/record.url?scp=0023839303&partnerID=8YFLogxK
U2 - 10.1016/S0092-8674(88)80026-6
DO - 10.1016/S0092-8674(88)80026-6
M3 - Article
C2 - 2964276
AN - SCOPUS:0023839303
SN - 0092-8674
VL - 52
SP - 329
EP - 341
JO - Cell
JF - Cell
IS - 3
ER -