The cytoplasmic tail of the mouse brown locus product determines intracellular stability and export from the endoplasmic reticulum.
Several melanosome membrane proteins have been identified, forming a family of proteins known as tyrosinase related proteins. Human TRP-1/gp75 is sorted to melanosomes through the endoplasmic reticulum and Golgi complex to the endocytic pathway, directed by a sorting signal located in the cytoplasmic tail. This hexapeptide cytoplasmic sequence, which is conserved in the tyrosinase related protein family and through vertebrate evolution, was shown to act also as a sorting signal in mouse gp75, confirming that its sorting and cellular retention function is conserved between human and mouse. The cytoplasmic tail influenced the rate and efficiency of intracellular transport of gp75 from the endoplasmic reticulum to the cis-Golgi. Deletion of 33 or 27 amino acids from the carboxyl end of the 38 amino acid cytoplasmic tail of gp75 caused retention and rapid degradation of the truncated gp75 in the endoplasmic reticulum. This defective movement could be fully corrected by extending the truncated tail with the unrelated cytoplasmic tail of the low density lipoprotein receptor. Thus, the cytoplasmic tail of mouse gp75 not only determines sorting to the endocytic/melanosomal compartment, but also controls export from the endoplasmic reticulum to Golgi.
Xu
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The Swim Across America Laboratory, Memorial Sloan-Kettering Cancer Center and Sloan-Kettering Division, Cornell University Graduate School of Medical Sciences, New York, New York 10021, USA.
Vijayasaradhi
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Houghton
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D000595:Amino Acid Sequence; D000818:Animals; D001692:Biological Transport / Q000502:physiology; D002460:Cell Line; D003593:Cytoplasm / Q000502:physiology*; D004355:Drug Stability; D004721:Endoplasmic Reticulum / Q000378:metabolism*; D007425:Intracellular Membranes / Q000378:metabolism*; D008562:Membrane Glycoproteins; D051379:Mice; D010088:Oxidoreductases; D011506:Proteins / Q000737:chemistry / Q000235:genetics / Q000502:physiology*; D011973:Receptors, LDL / Q000235:genetics; D015398:Signal Transduction / Q000502:physiology; D013347:Subcellular Fractions / Q000378:metabolism
D008562:Membrane Glycoproteins; D011506:Proteins; D011973:Receptors, LDL; D010088:Oxidoreductases; C489799:TYRP1 protein, human; C079621:Tyrp1 protein, mouse; C064056:tyrosinase-related protein-1