Tyrosinase-related protein-2 and -1 are trafficked on distinct routes in B16 melanoma cells.
Tyrosinase related protein (TRP)-1 and -2 regulate the main steps in melanin synthesis and are immune targets in skin cancer or autoimmune pigmentary disorders. We found that ionophore monensin (Mon) and the quaternary amine chloroquine (CQ) discriminate between the traffic routes of TRP-2 and TRP-1. TRP-2 N-glycan processing is interrupted by Mon between ER and trans-Golgi, whereas this process continues for TRP-1. Mature TRP-2 is diverted by CQ treatment to a degradation pathway which depends on functional vacuolar ATPases. Conversely, the subcellular distribution and stability of TRP-1 were not affected by CQ. We propose that TRP-2 is sorted and trafficked in the early secretory pathway with a cargo which does not include TRP-1; post Golgi, TRP-2 intersects the endocytic pathway following a route via early endosomes, possibly by rapid recycling from the plasma membrane. These data show that highly structural homologous glycoproteins use distinct trafficking pathways in the same cell.
Negroiu
Gabriela
G
Institute of Biochemistry of the Romanian Academy, Splaiul Independentei 296, 060031 Bucharest 17, Romania. gnegroiu@biochim.ro
Dwek
Raymond A
RA
Petrescu
Stefana M
SM
D000818:Animals; D045744:Cell Line, Tumor; D002738:Chloroquine / Q000494:pharmacology; D004721:Endoplasmic Reticulum / Q000187:drug effects / Q000378:metabolism; D006056:Golgi Apparatus / Q000187:drug effects / Q000378:metabolism; D019746:Intramolecular Oxidoreductases / Q000378:metabolism*; D008546:Melanoma, Experimental / Q000378:metabolism* / Q000473:pathology; D008562:Membrane Glycoproteins / Q000378:metabolism*; D051379:Mice; D008985:Monensin / Q000494:pharmacology; D010088:Oxidoreductases / Q000378:metabolism*; D021381:Protein Transport
D008562:Membrane Glycoproteins; D002738:Chloroquine; D008985:Monensin; D010088:Oxidoreductases; C489799:TYRP1 protein, human; D019746:Intramolecular Oxidoreductases; C042501:dopachrome isomerase