The melanosome: The perfect model for cellular responses to the environment

被引:97
作者
Hearing, VJ [1 ]
机构
[1] NCI, Pigment Cell Biol Sect, Cell Biol Lab, NIH, Bethesda, MD 20892 USA
来源
PIGMENT CELL RESEARCH | 2000年 / 13卷
关键词
melanin; pigmentation; photoabsorption; melanoma;
D O I
10.1034/j.1600-0749.13.s8.7.x
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
Melanocytes play critical roles in mammals, including the regulation of constitutive pigmentation in the skin, hair, and eyes, in embryological development, and in photoprotection from ionizing radiation. The pigments themselves, possibly due to the inherent cytotoxic properties of their precursors, are synthesized and deposited within membrane-bound organelles known as melanosomes, However, the structure of melanosomes, and thus their characteristic properties, varies widely, from relatively disorganized, poorly pigmented pheomelanosomes to highly structured, melanized eumelanosomes. Melanocytes respond to various physiological stimuli, such as melanocyte-stimulating hormone (MSH), agouti signal protein (ASP), endothelins and/or ultra violet light (UVL) by highly complex intracellular signaling mechanisms that can elicit dramatic changes in melanosome and melanocyte morphology. MSH and UVL stimulate transcription of melanogenic genes that elicit dramatic increases in the amount of eumelanins produced, whereas ASP serves as an antagonist of MSH and inhibits the transcription of those same genes. Recent studies have shown that melanocyte-specific transcription factors, such as MITF, play important roles in these responses, but ubiquitous transcription factors, such as ITF2 and E2A, are also involved. Virtually all known intracellular signaling pathways affect one or more parameters of pigmentation, and it is clear that both melanocyte-specific and basic housekeeping processes are affected by such modulation. The properties of melanins, including their photoprotective function, may be optimized by such stimulatory responses. Studies targeted at elucidating the regulatory mechanisms involved and the functional changes that result demonstrate that the melanosome is the perfect model to study such biological response mechanisms.
引用
收藏
页码:23 / 34
页数:12
相关论文
共 81 条
[1]   MITOGENIC AND MELANOGENIC STIMULATION OF NORMAL HUMAN MELANOCYTES BY MELANOTROPIC PEPTIDES [J].
ABDELMALEK, Z ;
SWOPE, VB ;
SUZUKI, I ;
AKCALI, C ;
HARRIGER, MD ;
BOYCE, ST ;
URABE, K ;
HEARING, VJ .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1995, 92 (05) :1789-1793
[2]   Involvement of microphthalmia in the inhibition of melanocyte lineage differentiation and of melanogenesis by agouti signal protein [J].
Aberdam, E ;
Bertolotto, C ;
Sviderskaya, EV ;
de Thillot, V ;
Hemesath, TJ ;
Fisher, DE ;
Bennett, DC ;
Ortonne, JP ;
Ballotti, R .
JOURNAL OF BIOLOGICAL CHEMISTRY, 1998, 273 (31) :19560-19565
[3]   The genetics of pigmentation: From fancy genes to complex traits [J].
Barsh, GS .
TRENDS IN GENETICS, 1996, 12 (08) :299-305
[4]   Different cis-acting elements are involved in the regulation of TRP1 and TRP2 promoter activities by cyclic AMP:: Pivotal role of M boxes (GTCATGTGCT) and of microphthalmia [J].
Bertolotto, C ;
Buscà, R ;
Abbe, P ;
Bille, K ;
Aberdam, E ;
Ortonne, JP ;
Ballotti, R .
MOLECULAR AND CELLULAR BIOLOGY, 1998, 18 (02) :694-702
[5]  
Boissy RE, 1996, AM J HUM GENET, V58, P1145
[6]   Human tyrosinase related protein-1 (TRP-1) does not function as a DHICA oxidase activity in contrast to murine TRP-1 [J].
Boissy, RE ;
Sakai, C ;
Zhao, HQ ;
Kobayashi, T ;
Hearing, VJ .
EXPERIMENTAL DERMATOLOGY, 1998, 7 (04) :198-204
[7]   Tyrosinase folding and copper loading in vivo:: A crucial role for calnexin and α-glucosidase II [J].
Branza-Nichita, N ;
Petrescu, AJ ;
Dwek, RA ;
Wormald, MR ;
Platt, FM ;
Petrescu, SM .
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 1999, 261 (03) :720-725
[8]   SUNLIGHT, MELANOGENESIS AND RADICALS IN THE SKIN [J].
CHEDEKEL, MR ;
ZEISE, L .
LIPIDS, 1988, 23 (06) :587-591
[9]  
deVries TJ, 1997, CANCER RES, V57, P3223
[10]   Conserved gene structure and genomic linkage for D-dopachrome tautomerase (DDT) and MIF [J].
Esumi, N ;
Budarf, M ;
Ciccarelli, L ;
Sellinger, B ;
Kozak, CA ;
Wistow, G .
MAMMALIAN GENOME, 1998, 9 (09) :753-757