Melanocyte-specific catalases as positive regulators of melanogenesis
Pigmentation is regulated to a large extent by the levels of tyrosinase activity as indicated by tyrosinase measurements in vitro. Surprisingly, therefore, approximately half of the human population of albinos is tyrosinase-positive (Witkop et al, 1983), an indication of the existence of additional regulatory factors that are operative in normal pigmentation but not in tyrosinase-positive albinism. In mice at least 50 genetic loci outside the tyrosinase-or c-locus are known to affect pigmentation (Silver, 1979), one of these being the brown or b-locus, but little is known about the molecular basis for any of these genetic coat color variations.
We have carried out immunoprecipitation studies using anti-tyrosinase antibodies. TMH-1
and anti-PEP1 antibodies to the brown-locus protein (Tomita et al, 1985; Jimenez et
al, 1988), demonstrating that two melanocyte-specific glycoproteins have catalase
activity. One of these, which we call catalase-Br, segregates with the murine brown coat
color locus, and the other, which we call P-catalase, does not. In human melanocytes the
abundance of immunoprecipitated catalase-Br correlates with the amount of melanin more so
than does tyrosinase. Because H202 may be a byproduct of tyrosinase
activity and is known to destroy melanin precursors, we conclude that pigmentation is
controlled not only by tyrosinase, but also by enzymes that decompose H202.
Thus, mutations that decrease the activities of these two catalases may be the reason for
the absence of eumelanin in red hair and tyrosinase-positive albinos.
Jimenez M et al: J Biol Chem 264:3397-3403.
Silver WK: The Coat Colors of Mice, Springer-Verlag, NY, 1979.
Tomita Y et al : J Invest Dermatol 85:426-430.
Witkop Jr CJ et al : In: Metabolic basis of inherited disease (Stanbury JB et al. eds), McGraw-Hill, NY, 301-346.
Ruth Halaban and Gisela Moellman
Dept of Dermatology
Yale University School of Medicine
500 LCI, PO Box 3333
New Haven, Connecticut 065:0-8059