More than 10% of admissions worldwide to institutions for the @entity227 are due to some form of @entity4068 . The most common form, @entity44677 , results from mutations at the p locus. The function of the p gene is yet to be determined. It has been shown that melanocytes from p -null @entity19 exhibit an abnormal melanosomal ultrastructure in addition to alterations in activity and localization of @entity22835 , a critical melanogenic enzyme. In light of these observations, we examined @entity22835 trafficking in p -null vs wildtype @entity19 melanocytes in order to explore p function. Electron microscopy of wildtype melan-a and p -null melan-p1 cells demonstrated accumulation of @entity22835 in 50 nm vesicles throughout the cell in the absence of p, an observation corroborated by an increase in @entity22835 activity in vesicle-enriched fractions from melan-p1 compared to melan-a cells. Misrouting in the absence of p was not limited to @entity22835 ; a second melanosomal protein, @entity22837 , also trafficked incorrectly. In melan-p1, mislocalization led to secretion of @entity22835 into the medium. Adding @entity669 to the medium was found to partially correct @entity22835 trafficking and to reduce secretion; the @entity462 protease inhibitor @entity19258 also reduced secretion. We propose that p is required by melanocytes for transport of melanosomal proteins. In its absence, @entity22835 accumulates in vesicles and, in cultured melanocytes, is proteolysed and secreted.

Mislocalization of melanosomal proteins in melanocytes from @entity19 with XXXX .

@entity227 :: ('MESH:D014786', 'Disease') :: ['visually impaired'] @entity462 :: ('MESH:D003545', 'Chemical') :: ['cysteine'] @entity44677 :: ('MESH:C537730', 'Disease') :: ['oculocutaneous albinism type 2'] @entity19 :: ('10090', 'Species') :: ['mice', 'mouse'] @entity22837 :: ('22178(Tax:10090)', 'Gene') :: ['tyrosinase-related protein 1'] @entity19258 :: ('CHEBI:30270', 'Chemical') :: ['E64'] @entity4068 :: ('MESH:D000417', 'Disease') :: ['albinism'] @entity669 :: ('CHEBI:18186', 'Chemical') :: ['tyrosine'] @entity22835 :: ('22173(Tax:10090)', 'Gene') :: ['tyrosinase']
@entity44677 :: (MESH:C537730,Disease) :: ['oculocutaneous albinism type 2']
