Rapid transport of internalized P-selectin to late endosomes and the TGN: roles in regulating cell surface expression and recycling to secretory granules.
Prior studies on receptor recycling through late endosomes and the TGN have suggested that such traffic may be largely limited to specialized proteins that reside in these organelles. We present evidence that efficient recycling along this pathway is functionally important for nonresident proteins. P-selectin, a transmembrane cell adhesion protein involved in inflammation, is sorted from recycling cell surface receptors (e.g., low density lipoprotein [LDL] receptor) in endosomes, and is transported from the cell surface to the TGN with a half-time of 20-25 min, six to seven times faster than LDL receptor. Native P-selectin colocalizes with LDL, which is efficiently transported to lysosomes, for 20 min after internalization, but a deletion mutant deficient in endosomal sorting activity rapidly separates from the LDL pathway. Thus, P-selectin is sorted from LDL receptor in early endosomes, driving P-selectin rapidly into late endosomes. P-selectin then recycles to the TGN as efficiently as other receptors. Thus, the primary effect of early endosomal sorting of P-selectin is its rapid delivery to the TGN, with rapid turnover in lysosomes a secondary effect of frequent passage through late endosomes. This endosomal sorting event provides a mechanism for efficiently recycling secretory granule membrane proteins and, more generally, for downregulating cell surface receptors.
Straley
K S
KS
Department of Cell Biology, University of Virginia Health System, School of Medicine, Charlottesville, Virginia 22908-0732, USA.
Green
S A
SA
D000818:Animals; D002462:Cell Membrane; D004705:Endocytosis; D011992:Endosomes / Q000378:metabolism*; D005455:Fluorescent Antibody Technique; D008360:Mannosephosphates / Q000378:metabolism; D008954:Models, Biological; D009004:Monosaccharide Transport Proteins / Q000378:metabolism; D019007:P-Selectin / Q000378:metabolism*; D016716:PC12 Cells; D021381:Protein Transport; D051381:Rats; D011973:Receptors, LDL / Q000378:metabolism; D022142:Secretory Vesicles / Q000378:metabolism*; D016708:Synaptophysin; D021601:trans-Golgi Network / Q000378:metabolism*
D008360:Mannosephosphates; D009004:Monosaccharide Transport Proteins; D019007:P-Selectin; D011973:Receptors, LDL; D016708:Synaptophysin; C027693:mannose-6-phosphate