Tyrosinase Maturation and Oligomerization in the Endoplasmic Reticulum Require a Melanocyte-specific Factor

Tyrosinase is a glycoprotein responsible for the synthesis of melanin in melanocytes. A large number of mutations have been identified in tyrosinase, with many leading to its misfolding, endoplasmic reticulum (ER) retention, and degradation. Here we describe the folding and maturation of human tyrosinase (TYR) using an in vitro translation system coupled with ER-derived microsomes or with semipermeabilized cells, an its to and its with the and in ER-derived microsomes or semipermeabilized semipermeabilized maturation to a and a of semipermeabilized for tyrosinase or the maturation and the of tyrosinase and is a in maturation the Tyrosinase is a glycoprotein responsible for the synthesis of melanin in melanocytes. A large number of mutations have been identified in tyrosinase, with many leading to its misfolding, endoplasmic reticulum (ER) retention, and degradation. Here we describe the folding and maturation of human tyrosinase (TYR) using an in vitro translation system coupled with ER-derived microsomes or with semipermeabilized cells, an its to and its with the and in ER-derived microsomes or semipermeabilized semipermeabilized maturation to a and a of semipermeabilized for tyrosinase or the maturation and the of tyrosinase and is a in maturation the Tyrosinase the in melanin glycoprotein is to the the in tyrosinase the of tyrosinase is a the system of the endoplasmic reticulum endoplasmic human endoplasmic human is for tyrosinase in is in the in to an of and is to Tyrosinase been a to glycoprotein maturation in the of its with human and the in its the of the tyrosinase, a the of the the the is a maturation of the maturation and and maturation for the of the of with and the of tyrosinase (TYR) is to an of is in tyrosinase a of or and in for and of and with to for its maturation and the of its the of in human and tyrosinase in with of the the of and the of the to the a semipermeabilized system coupled with in vitro the and of system a of the to and the for to a and and and and and and and in the or in of of and of of and in in in of and of the been the and the in to and using the of a in of the mutations and in vitro the with for with or in the of microsomes or semipermeabilized the with or with in to of or with of the to and the the of of the with of a of and in of for in and with for the of in for and for in and with a for to the for and in to a of for in with semipermeabilized for the ER-derived the of the and with semipermeabilized in in and in a for and the of a in with in a for to with and in with to its maturation and with for or semipermeabilized in translation and to of for with and the or in and of the to with for with with with and to with in system to the maturation of in the have and of in a system of an in vitro translation system coupled with ER-derived microsomes the of with of the the of translation and been the and is to the of in the in or translation with ER-derived of synthesis with and the to for of of with the and or with and and (TYR) a to or the of in the system with the in the a in of a the of the of the maturation system is the of is to the an with an of for a of the the the of the of with a in or in in the of ER-derived microsomes or with or A large in of and the in to in of the to in of the translation system or in to in the to or with and the in ER-derived microsomes with of with or with of of the system and for the of and the microsomes system the maturation of the glycoprotein in is a is a to is for its we a semipermeabilized system coupled to the in vitro translation of a of with semipermeabilized with a an have semipermeabilized system the and of the of semipermeabilized or with or in the semipermeabilized a in with and of of A with a of of in with and in semipermeabilized melanocytes. in in the of to for of with or and and for the in the of microsomes or semipermeabilized of the and with for and a and translation and or and the of and for maturation in semipermeabilized the of to the of the of of maturation the and is a is the is of its and is of or the of an in with to an for maturation a is to of in the system the of of maturation a of of a to semipermeabilized to the folding of in the and in the for and the of synthesis with of of the maturation for in semipermeabilized of the in the of semipermeabilized with the and to a of in the and to in of of of the of an a of with the is in in of tyrosinase in and a with and maturation for and the to of a in and to a and of with the of the of the and the of the of of the of and and in the maturation of in semipermeabilized in the of and of and of or and of in a to the of with and in the of the with in the of the of for in the of semipermeabilized for the or of or to with or and and in tyrosinase the of a the of melanin in of in to folding is for and to the responsible for in the is in the an to the and is with a of and is the and in in is with to maturation to of the of the a of the of the with to the in a to of to been in and in the is in the semipermeabilized system the the in its of and of and and and in the of semipermeabilized to the and with or and in the for to in the of the in we the in or of a an maturation the in the to folding the of a the the and for we the maturation of a in to a to the and in in or in tyrosinase the of an in the is the and in human have been to a maturation of the for the maturation of in semipermeabilized and of maturation in semipermeabilized and the maturation in or semipermeabilized of is in in the of semipermeabilized or or to and the for with or and the of with maturation in the in to in the of with in the semipermeabilized cells, a to in to in semipermeabilized human and its to folding and maturation of with the or in semipermeabilized tyrosinase the cells, or for Tyrosinase of mutations in the of tyrosinase and its and in maturation in or of is in or and with in the of semipermeabilized tyrosinase and or and the of of to with or and and in vitro maturation in semipermeabilized the for and in semipermeabilized in the an and the a for the in the with the of folding in the and is in the in vitro translation and semipermeabilized the the in an in the the of the the of is to the with semipermeabilized in we the a with to and with and the with A tyrosinase of in and tyrosinase in to the human in the semipermeabilized system using melanocytes. of tyrosinase in a large with folding of tyrosinase the of a number of and a number of for the for with of for the the of the in the of in the tyrosinase to a in of tyrosinase in melanocytes. and with the and and with Tyrosinase with in a semipermeabilized system the of the maturation for and of and the the in vitro translation of system the the to the the of to maturation to in the for the the in the maturation the in vitro semipermeabilized system of to the and in a in and a folding the of to the the of maturation in the is an we identified in the of the for the to in its for and for a in cells, the of the an the in in the been in the of in vitro the of a the of semipermeabilized with the a the of the or the of the of to an the of an the with tyrosinase in of the a and a with a the a to the with a of to in a with the of and to with is with a for in for to in its is in with the tyrosinase a in we the the the using semipermeabilized the for in vitro for using of ER-derived microsomes a with and to and the for semipermeabilized for to in an and of human in semipermeabilized in a to the for its and the of the with mutations in the tyrosinase is to the and a is in the in and of in semipermeabilized in semipermeabilized is its of in human and maturation in the and its to the of with the in an the in vitro system with to to in the semipermeabilized with and in with tyrosinase is in for a for in the maturation of the the of to in the of semipermeabilized its maturation and is the of the its human to the the an to a the the tyrosinase the for human of the in to of in in maturation and to the is tyrosinase is in large in and the the in of in the of in tyrosinase is in melanocytes. is to the of to in the of the for melanin to in using and is for or the of is with with the glycoprotein its folding and for of the of of a for the in the of the maturation of and in been to melanin tyrosinase to to tyrosinase in the folding of the and the of in the the its the of the is in the and or is and a is or in to the with the with the for and in semipermeabilized or and with in semipermeabilized and a and the in the and for the the a been a the and for is a its is the of a to the the of the to its to is with to the and degradation. to the in vitro system in a of an of the the the of in the of the the of semipermeabilized we have been to a of the maturation for tyrosinase and with the maturation of in vitro system of the in and of to the to in and Tyrosinase the in melanin glycoprotein is to the the in tyrosinase the of tyrosinase is a the system of the endoplasmic reticulum endoplasmic human endoplasmic human is for tyrosinase in is in the in to an of and is to Tyrosinase been a to glycoprotein maturation in the of its with human and the in its the of the tyrosinase, a the of the the the is a maturation of the maturation and and maturation for the of the of with and the of tyrosinase (TYR) is to an of is in tyrosinase a of or and in for and of and with to for its maturation and the of its the of in human and tyrosinase in with of the the of and the of the to the a semipermeabilized system coupled with in vitro the and of system a of the to and the for to a and and and and and and and in the or in of of and of of and in in in of and of the been the and the in to and using the of a in of the mutations and in vitro the with for with or in the of microsomes or semipermeabilized the with or with in to of or with of the to and the the of of the with of a of and in of for in and with for the of in for and for in and with a for to the for and in to a of for in with semipermeabilized for the ER-derived the of the and with semipermeabilized in in and in a for and the of a in with in a for to with and in with to its maturation and with for or semipermeabilized in translation and to of for with and the or in and of the to with for with with with and to with and and and and and and in the or in of of and of of and in in in of and of the been the and the in to and using the of a in of the mutations and in vitro the with for with or in the of microsomes or semipermeabilized the with or with in to of or with of the to and the the of of the with of a of and in of for in and with for the of in for and for in and with a for to the for and in to a of for in with semipermeabilized for the ER-derived the of the and with semipermeabilized in in and in a for and the of a in with in a for to with and in with to its maturation and with for or semipermeabilized in translation and to of for with and the or in and of the to with for with with with and to with in system to the maturation of in the have and of in a system of an in vitro translation system coupled with ER-derived microsomes the of with of the the of translation and been the and is to the of in the in or translation with ER-derived of synthesis with and the to for of of with the and or with and and (TYR) a to or the of in the system with the in the a in of a the of the of the maturation system is the of is to the an with an of for a of the the the of the of with a in or in in the of ER-derived microsomes or with or A large in of and the in to in of the to in of the translation system or in to in the to or with and the in ER-derived microsomes with of with or with of of the system and for the of and the microsomes system the maturation of the glycoprotein in is a is a to is for its we a semipermeabilized system coupled to the in vitro translation of a of with semipermeabilized with a an have semipermeabilized system the and of the of semipermeabilized or with or in the semipermeabilized a in with and of of A with a of of in with for maturation in semipermeabilized the of to the of the of of maturation the and is a is the is of its and is of or the of an in with to an for maturation a is to of in the system the of of maturation a of of a to semipermeabilized to the folding of in the and in the for and the of synthesis with of of the maturation for in semipermeabilized of the in the of semipermeabilized with the and to a of in the and to in of of of the of an a of with the is in in of tyrosinase in and a with and maturation for and the to of a in and to a and of with the of the of the and the of the of of the of and and in the maturation of in semipermeabilized in the of and of and of or and of in a to the of with and in the of the with in the of the of for in the of semipermeabilized for the or of or to with or and and in tyrosinase the of a the of melanin in of in to folding is for and to the responsible for in the is in the an to the and is with a of and is the and in in is with to maturation to of the of the a of the of the with to the in a to of to been in and in the is in the semipermeabilized system the the in its of and of and and and in the of semipermeabilized to the and with or and in the for to in the of the in we the in or of a an maturation the in the to folding the of a the the and for we the maturation of a in to a to the and in in or in tyrosinase the of an in the is the and in human have been to a maturation of the for the maturation of in semipermeabilized and of maturation in semipermeabilized and the maturation in or semipermeabilized of is in in the of semipermeabilized or or to and the for with or and the of with maturation in the in to in the of with in the semipermeabilized cells, a to in to in semipermeabilized human and its to folding and maturation of with the or in semipermeabilized tyrosinase the cells, or for Tyrosinase of mutations in the of tyrosinase and its and in maturation in or of is in or and with in the of semipermeabilized tyrosinase and or and the of of to with or and and in vitro maturation in semipermeabilized the for and in semipermeabilized in the an and the a for the in the with the of folding in the and is in the in vitro translation and semipermeabilized the the in an in the the of the the of is to the with semipermeabilized in we the a with to and with and the with A tyrosinase of in and tyrosinase in to the human in the semipermeabilized system using melanocytes. of tyrosinase in a large with folding of tyrosinase the of a number of and a number of for the for with of for the the of the in the of in the tyrosinase to a in of tyrosinase in melanocytes. and with the and and with Tyrosinase with in in system to the maturation of in the have and of in a system of an in vitro translation system coupled with ER-derived microsomes the of with of the the of translation and been the and is to the of in the in or translation with ER-derived of synthesis with and the to for of of with the and or with and and (TYR) a to or the of in the system with the in the a in of a the of the of the maturation system is the of is to the an with an of for a of the the the of the of with a in or in in the of ER-derived microsomes or with or A large in of and the in to in of the to in of the translation system or in to in the to or with and the in ER-derived microsomes with of with or with of of the system and for the of and the microsomes system the maturation of the glycoprotein in is a is a to is for its we a semipermeabilized system coupled to the in vitro translation of a of with semipermeabilized with a an have semipermeabilized system the and of the of semipermeabilized or with or in the semipermeabilized a in with and of of A with a of of in with for maturation in semipermeabilized the of to the of the of of maturation the and is a is the is of its and is of or the of an in with to an for maturation a is to of in the system the of of maturation a of of a to semipermeabilized to the folding of in the and in the for and the of synthesis with of of the maturation for in semipermeabilized of the in the of semipermeabilized with the and to a of in the and to in of of of the of an a of with the is in in maturation for and the to of a in and to a and of with the of the of the and the of the of of the of and and in the maturation of in semipermeabilized in the of and of and of or and of in a to the of with and in the of the with in the of the of for in tyrosinase the of a the of melanin in of in to folding is for and to the responsible for in the is in the an to the and is with a of and is the and in in is with to maturation to of the of the a of the of the with to the in a to of to been in and in the is in the semipermeabilized system the the in the for to in the of the in we the in or of a an maturation the in the to folding the of a the the and for we the maturation of a in to a to the and in in or in tyrosinase the of an in the is the and in human have been to a maturation of the for the maturation of in semipermeabilized and of maturation in semipermeabilized and the maturation in or semipermeabilized of with maturation in the in to in the of with in the semipermeabilized cells, a to in to in semipermeabilized human and its to folding and maturation of with the or in semipermeabilized tyrosinase the cells, or for Tyrosinase of mutations in the of tyrosinase and its and in maturation in or and in vitro maturation in semipermeabilized the for and in semipermeabilized in the an and the a for the in the with the of folding in the and is in the in vitro translation and semipermeabilized the the in an in the the of the the of is to the with semipermeabilized in we the a with to and with and the with A tyrosinase of in and tyrosinase in to the human in the semipermeabilized system using melanocytes. of tyrosinase in a large with folding of tyrosinase the of a number of and a number of for the for with of for the the of the in the of in the tyrosinase to a in a semipermeabilized system the of the maturation for and of and the the in vitro translation of system the the to the the of to maturation to in the for the the in the maturation the in vitro semipermeabilized system of to the and in a in and a folding the of to the the of maturation in the is an we identified in the of the for the to in its for and for a in cells, the of the an the in in the been in the of in vitro the of a the of semipermeabilized with the a the of the or the of the of to an the of an the with tyrosinase in of the a and a with a the a to the with a of to in a with the of and to with is with a for in for to in its is in with the tyrosinase a in we the the the using semipermeabilized the for in vitro for using of ER-derived microsomes a with and to and the for semipermeabilized for to in an and of human in semipermeabilized in a to the for its and the of the with mutations in the tyrosinase is to the and a is in the in and of in semipermeabilized in semipermeabilized is its of in human and maturation in the and its to the of with the in an the in vitro system with to to in the semipermeabilized with and in with tyrosinase is in for a for in the maturation of the the of to in the of semipermeabilized its maturation and is the of the its human to the the an to a the the tyrosinase the for human of the in to of in in maturation and to the is tyrosinase is in large in and the the in of in the of in tyrosinase is in melanocytes. is to the of to in the of the for melanin to in using and is for or the of is with with the glycoprotein its folding and for of the of of a for the in the of the maturation of and in been to melanin tyrosinase to to tyrosinase in the folding of the and the of in the the its the of the is in the and or is and a is or in to the with the with the for and in semipermeabilized or and with in semipermeabilized and a and the in the and for the the a been a the and for is a its is the of a to the the of the to its to is with to the and degradation. to the in vitro system in a of an of the the the of in the of the the of semipermeabilized we have been to a of the maturation for tyrosinase and with the maturation of in vitro system of the in and of to the to in and a semipermeabilized system the of the maturation for and of and the the in vitro translation of system the the to the the of to maturation to in the for the the in the maturation the in vitro semipermeabilized system of to the and in a in and a folding the of to the the of maturation in the is an we identified in the of the for the to in its for and for a in cells, the of the an the in in the been in the of in vitro the of a the of semipermeabilized with the a the of the or the of the of to an the of an the with tyrosinase in of the a and a with a the a to the with a of to in a with the of and to with is with a for in for to in its is in with the tyrosinase a in we the the the using semipermeabilized the for in vitro for using of ER-derived microsomes a with and to and the for semipermeabilized for to in an to the for its and the of the with mutations in the tyrosinase is to the and a is in the in and of in semipermeabilized in semipermeabilized melanocytes. is its of in human and maturation in the and its to the of with the in an the in vitro system with to to in the semipermeabilized with and in with tyrosinase is in for a for in the maturation of the the of to in the of semipermeabilized its maturation and is the of the its human to the the an to a the the tyrosinase the for human of the in to of in in maturation and to the is tyrosinase is in large in and the the in of in the of in tyrosinase is in melanocytes. is to the of to in the of the for melanin to in using and is for or the of is with with the glycoprotein its folding and for of the of of a for the in the of the maturation of and in been to melanin tyrosinase to to tyrosinase in the folding of the and the of in the the its the of the is in the and or is and a is or in to the with the with the for and in semipermeabilized or and with in semipermeabilized and a and the in the and for the the a been a the and for is a its is the of a to the the of the to its to is with to the and degradation. to the in vitro system in a of an of the the the of in the of the the of semipermeabilized we have been to a of the maturation for tyrosinase and with the maturation of in vitro system of the in and of to the to in and and for the and and for the in