Melanins And Melanosomes - Biosynthesis, Structure, Physiological And Pathological Functions

The surface pigmentation of vertebrates is controlled by specialized cells able to synthesize a variety of pigments collectively known as melanins. Recent research has shown that melanins are produced not only in the skin but also in many other sites such as the eye, inner ear, muscles, etc., - where they are engaged in some unanticipated roles. The details of the synthetic pathway, the complexities of its regulation and biological significance that have been unravelled in recent research comprise a fascinating story and are of key importance in understanding the nature of diseases, including malignant melanoma one of the most rapidly spreading cancers.

Patrick Riley was born in Paris in 1935 and was educated in Zurich and at King Edward VII School, King?s Lynn. He graduated from University College Hospital Medical School in 1960 and gained his Ph.D. from the Department of Dermatological Histopathology under Arthur Jarrett. He joined the Department of Claude Rimington and began a series of cellular studies culminating in his appointment to a Chair of Cell Pathology at UCL in 1984. His work covered many fundamental aspects of cell pathology including free radical pathology, cell size control, regulation of cell proliferation and cancer. Patrick Riley was a founder member of the European Society for Pigment Cell Research and the International Federation of Pigment Cell Societies. He was the organiser and Chairman of the XVth International Pigment Cell Conference. He was the recipient of the Myron Gordon Award in 1993 and the Centenary Medal of Charles University. He has published extensively on melanocytes, melanogenesis and melanoma. He was joint Charman with Jan Borovansky of the recent FEBS Symposium on Melanins and Melanogenesis.

Jan Borovansky was born in Prague in 1943. He graduated from Faculty of General Medicine, Charles University in 1966 and gained his Ph.D. in 1976 from the Department of Medical Chemistry and Biochemistry under Professor J. Duchon. From 1970 to 1980 he was Lecturer in Medical Chemistry and Biochemistry. In 1980 he defended his Habilitation Thesis and became Associate Professor at the Charles University, and in 2004 he was appointed a Full Professor of Biochemistry. In 2008 he was elected to the Senate of the 1st Faculty of Medicine, Charles University, Prague. From the outset of his research career he has been involved in biochemical studies of melanosomes, and the enzymes associated with them. He has also published important studies on metal binding by melanins, the cytotoxicity of zinc, and free radical processes in normal and malignant pigment cells. Since 1979 he has been member of the International Pigment Cell Society and following its transformation into European Society for Pigment Cell Research (ESPCR) he was elected to its Council (1990-1998). In 1981 he was General Secretary of the 3rd European Workshop on Melanin Pigmentation and in 1998 he was President of the 8th Meeting of the ESPCR organized in Prague. As a long-standing member of the Editorial Board of Pigment Cell Research (1995-1998) he received a special Certificate of Appreciation from the International Federation of Pigment Cell Societies and Munksgaard in 1999. Since 2000 he has been a member of the International Board of the Pigment Cell Research Bulletin to which he regularly contributes with critical bibliographical reviews concerning melanosomes. He is a member of the Editorial Board of Folia Biologica (Prague) (2006-present) and a member of the Board of Advisors of the American Biographical Institute. He was an Honorary Research Fellow at University College London (1980, 1984) and has been a Visiting Scientist at several other institutions including Sheffield University (1978) and Leiden University Medical Centre (1997). He was the recipient of the Annual award of the Czechoslovak Oncological Society in 1975. Recently, he was appointed a member of the Organizing Committee of the 34th FEBS Meeting held in Prague and was responsible for planning the Symposium on Melanins and Melanogenesis

Dedication.

Preface.

List of Contributors.

1 History of Melanosome Research (Jan Borovansky).

1.1 Introduction.

1.2 Melanosome Research in the Pre-Seiji Era.

1.3 Melanosome Research in the Seiji Era.

1.4 Melanosome Research in the Post-Seiji Era.

1.5 Other Historical Aspects.

Acknowledgments.

References.

2 Classical and Nonclassical Melanocytes in Vertebrates (Sophie Colombo, Irina Berlin, Veronique Delmas, and Lionel Larue).

2.1 Defi nition of Melanogenic Cells.

2.2 Distribution and Function of Melanogenic Cells.

2.3 Embryonic Development of Melanogenic Cells.

2.4 Transfer of Melanin from Classical and Nonclassical Melanocytes.

3 Biological Chemistry of o-Quinones (Patrick A. Riley, Christopher A. Ramsden, and Edward J. Land).

3.1 General Biological Signifi cance of o-Quinones.

3.2 o-Quinone Reactivity.

3.3 Role of o-Quinones in Melanogenesis.

4 Biosynthesis of Melanins (Jose Carlos Garcia-Borron and M. Concepcion Olivares Sanchez).

4.1 Introduction.

4.2 Raper–Mason Pathway.

4.3 Structural and Functional Properties of the Melanogenic Enzymes.

4.4 Regulation of the Melanogenic Pathway.

4.5 Conclusions and Perspectives.

Acknowledgments.

References.

5 Inhibitors and Enhancers of Melanogenesis (Alain Taieb, Muriel Cario-Andre, Stefania Briganti, and Mauro Picardo).

5.1 Introduction.

5.2 Depigmenting Agents.

5.3 Enhancers of Melanogenesis.

6 Structure of Melanins (Shosuke Ito, Kazumasa Wakamatsu, Marco d’Ischia, Alessandra Napolitano, and Alessandro Pezzella).

6.1 Introduction.

6.2 Classification and General Properties of Melanins.

6.3 Biosynthetic Studies.

6.4 Degradative Studies.

6.5 Analysis of Eumelanins and Pheomelanins.

6.6 Conclusions.

References.

7 Properties and Functions of Ocular Melanins and Melanosomes (Małgorzata Rozanowska).

7.1 Introduction.

7.2 Biogenesis of Ocular Melanosomes and Melanogenesis.

7.3 Melanin Content in Pigmented Structures of the Eye.

7.4 Structure of Ocular Melanosomes.

7.5 Role of Ocular Melanin as a Broadband Optical Filter.

7.6 Antioxidant Properties of Ocular Melanin.

7.7 Pro-Oxidant Properties of Ocular Melanosomes.

7.8 Other Properties of Ocular Melanosomes and Their Implications.

7.9 Conclusions.

References.

8 Biological Role of Neuromelanin in the Human Brain and Its Importance in Parkinson’s Disease (Kay L. Double, Wakako Maruyama, Makoko Naoi, Manfred Gerlach, and Peter Riederer).

8.1 What are Neuromelanins?

8.2 Phylogenetic Development of Neuromelanin.

8.3 Development and Metabolism of Neuromelanin.

8.4 Structure of Neuromelanin.

8.5 Biological Role of Neuromelanin in the Human Brain.

8.6 Is Neuromelanin Involved in Neurological Disease?

8.7 Effects of Neuromelanin In Vitro and In Vivo.

8.8 Conclusions.

Acknowledgments.

References.

9 Biogenesis of Melanosomes (Cedric Delevoye, Francesca Giordano, Michael S. Marks, and Graca Raposo).

9.1 Introduction.

9.2 Melanosomes: Intracellular Organelles Specialized in Melanin Synthesis.

9.3 Endocytic System and Formation of Melanosomes.

9.4 Melanosome Maturation: Cargo Sorting to Mature Melanosomes.

9.5 Conclusions.

Acknowledgments.

References.

10 Transport and Distribution of Melanosomes (Mireille Van Gele and Jo Lambert).

10.1 Introduction.

10.2 Model Systems to Study Pigment Transport.

10.3 Intracellular Melanosome Transport.

10.4 Melanosome Motility in RPE: The Rab27a–Myrip–Myo7a Tripartite Complex.

10.5 Melanosome Transfer.

10.6 Fate of Melanin in the Keratinocyte.

10.7 Conclusions.

Acknowledgments.

References.

11 Genetics of Melanosome Structure and Function (Vincent J. Hearing).

11.1 Introduction.

11.2 Genes Involved in Melanoblast Development, Migration, and Specification.

11.3 Genes Involved in Melanocyte Differentiation, Survival, and Proliferation.

11.4 Genes Involved in Regulating Melanocyte Function.

11.5 Genes Involved in the Biogenesis of Melanosomes and Other Lysosome-Related Organelles.

11.6 Genes Involved in Melanin Production.

11.7 Genes Involved in Melanosome Movement, Transfer, and Distribution.

11.8 Conclusions.

References.

12 Physiological and Pathological Functions of Melanosomes (Jan Borovansky and Patrick A. Riley).

12.1 Tissue Concentration of Melanosomes.

12.2 Melanosome Properties and Functions Are Determined by Their Chemical Composition.

12.3 Functional Microanatomy of the Melanosome.

12.4 Melanosomes as Centers of Free Radical Activity.

12.5 Melanosomes as Energy Transducers.

12.6 Melanosomes and Metal Ions.

12.7 Affinity of Melanosomes for Polycyclic and Other Compounds.

12.8 Exploitation of Melanosomal Proteins and Melanin as Specific Targets in Melanoma Therapy.

12.9 Conclusions.

Acknowledgments.

References.

13 Dysplastic Nevi as Precursor Melanoma Lesions (Stanislav Pavel, Nico P.M. Smit, and Karel Pizinger).

13.1 Nevi as Risk Factors for Melanoma.

13.2 Dysplastic Nevi as Precursor Lesions of Melanoma.

13.3 Cytological Differences between Normal Skin Melanocytes and Dysplastic Nevus Cells: Melanosomal and Mitochondrial Aberrations.

13.4 Metabolic Differences between Normal Skin Melanocytes and Dysplastic Nevus Cells: Preference for Pheomelanogenesis in Dysplastic Nevus Cells.

13.5 Pheomelanogenesis as a Possible Cause of Intracellular Oxidative Imbalance.

13.6 Dysplastic Nevus Cells as Senescent Cells.

13.7 Are Dysplastic Nevus Cells a Class of Cells Exhibiting a Mutator Phenotype?

References.

Index.