Note to users. If you're seeing this message, it means that your browser cannot find this page's style/presentation instructions -- or possibly that you are using a browser that does not support current Web standards. Find out more about why this message is appearing, and what you can do to make your experience of our site the best it can be.

Site Tools

  • AAAS
  • Subscribe
  • Feedback

Site Search

Search Advanced

Science 2 July 2004:
Vol. 305. no. 5680, pp. 55 - 59
DOI: 10.1126/science.1095291
Prev | Table of Contents | Next

Review

Linking Albinism and Immunity: The Secrets of Secretory Lysosomes

Jane Stinchcombe, Giovanna Bossi, Gillian M. Griffiths*

Lysosomes are membrane-bound organelles that are found in all mammalian cells and contain hydrolases and lipases required for protein and membrane degradation. In many cells of the immune system, lysosomes also contain secretory proteins that can be released by regulated exocytosis in response to an external stimulus, providing different cell types with a wide range of effector functions. Melanosomes also use a lysosome-related organelle to secrete melanin for pigmentation. Links between albinism and immunity in patients have uncovered a number of key proteins required for lysosomal secretion and have revealed a versatile secretory mechanism that can be fine-tuned by distinct interactions in different cell types.

Sir William Dunn School of Pathology, South Parks Road, Oxford OX1 3RE, UK.

* To whom correspondence should be addressed. E-mail: gillian.griffiths{at}path.ox.ac.uk

Read the Full Text


THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES:
The Activation of P2X7 Receptor Impairs Lysosomal Functions and Stimulates the Release of Autophagolysosomes in Microglial Cells.
T. Takenouchi, M. Nakai, Y. Iwamaru, S. Sugama, M. Tsukimoto, M. Fujita, J. Wei, A. Sekigawa, M. Sato, S. Kojima, et al. (2009)
J. Immunol. 182, 2051-2062
   Abstract »    Full Text »    PDF »
Jakmip1 Is Expressed upon T Cell Differentiation and Has an Inhibitory Function in Cytotoxic T Lymphocytes.
V. Libri, D. Schulte, A. van Stijn, J. Ragimbeau, L. Rogge, and S. Pellegrini (2008)
J. Immunol. 181, 5847-5856
   Abstract »    Full Text »    PDF »
Rab27a Regulates Exocytosis of Tertiary and Specific Granules in Human Neutrophils.
M. J. Herrero-Turrion, J. Calafat, H. Janssen, M. Fukuda, and F. Mollinedo (2008)
J. Immunol. 181, 3793-3803
   Abstract »    Full Text »    PDF »
PI5KI-dependent signals are critical regulators of the cytolytic secretory pathway.
F. Micucci, C. Capuano, E. Marchetti, M. Piccoli, L. Frati, A. Santoni, and R. Galandrini (2008)
Blood 111, 4165-4172
   Abstract »    Full Text »    PDF »
Doc2{alpha} and Munc13-4 Regulate Ca2+-Dependent Secretory Lysosome Exocytosis in Mast Cells.
H. Higashio, N. Nishimura, H. Ishizaki, J. Miyoshi, S. Orita, A. Sakane, and T. Sasaki (2008)
J. Immunol. 180, 4774-4784
   Abstract »    Full Text »    PDF »
The zebrafish mutant lbk/vam6 resembles human multisystemic disorders caused by aberrant trafficking of endosomal vesicles.
H. B. Schonthaler, V. C. Fleisch, O. Biehlmaier, Y. Makhankov, O. Rinner, R. Bahadori, R. Geisler, H. Schwarz, S. C. F. Neuhauss, and R. Dahm (2008)
Development 135, 387-399
   Abstract »    Full Text »    PDF »
Formation and function of Weibel-Palade bodies.
D. J. Metcalf, T. D. Nightingale, H. L. Zenner, W. W. Lui-Roberts, and D. F. Cutler (2008)
J. Cell Sci. 121, 19-27
   Abstract »    Full Text »    PDF »
Identification of Genes Involved in the Toxic Response of Saccharomyces cerevisiae against Iron and Copper Overload by Parallel Analysis of Deletion Mutants.
W. J. Jo, A. Loguinov, M. Chang, H. Wintz, C. Nislow, A. P. Arkin, G. Giaever, and C. D. Vulpe (2008)
Toxicol. Sci. 101, 140-151
   Abstract »    Full Text »    PDF »
Genotype phenotype study of familial haemophagocytic lymphohistiocytosis due to perforin mutations.
A Trizzino, U z. Stadt, I Ueda, K Risma, G Janka, E Ishii, K Beutel, J Sumegi, S Cannella, D Pende, et al. (2008)
J. Med. Genet. 45, 15-21
   Abstract »    Full Text »    PDF »
Cutting Edge: Syntaxin 11 Regulates Lymphocyte-Mediated Secretion and Cytotoxicity.
L. N. Arneson, A. Brickshawana, C. M. Segovis, R. A. Schoon, C. J. Dick, and P. J. Leibson (2007)
J. Immunol. 179, 3397-3401
   Abstract »    Full Text »    PDF »
Resolving vesicle fusion from lysis to monitor calcium-triggered lysosomal exocytosis in astrocytes.
J. K. Jaiswal, M. Fix, T. Takano, M. Nedergaard, and S. M. Simon (2007)
PNAS 104, 14151-14156
   Abstract »    Full Text »    PDF »
Private Lives: Reflections and Challenges in Understanding the Cell Biology of the Immune System.
I. Mellman (2007)
Science 317, 625-627
   Abstract »    Full Text »    PDF »
A LYST/beige homolog is involved in biogenesis of Dictyostelium secretory lysosomes.
S. J. Charette and P. Cosson (2007)
J. Cell Sci. 120, 2338-2343
   Abstract »    Full Text »    PDF »
Jinx, an MCMV susceptibility phenotype caused by disruption of Unc13d: a mouse model of type 3 familial hemophagocytic lymphohistiocytosis.
K. Crozat, K. Hoebe, S. Ugolini, N. A. Hong, E. Janssen, S. Rutschmann, S. Mudd, S. Sovath, E. Vivier, and B. Beutler (2007)
J. Exp. Med. 204, 853-863
   Abstract »    Full Text »    PDF »
Differential dynamics of Rab3A and Rab27A on secretory granules.
M. T. W. Handley, L. P. Haynes, and R. D. Burgoyne (2007)
J. Cell Sci. 120, 973-984
   Abstract »    Full Text »    PDF »
Function of the Caenorhabditis elegans ABC Transporter PGP-2 in the Biogenesis of a Lysosome-related Fat Storage Organelle.
L. K. Schroeder, S. Kremer, M. J. Kramer, E. Currie, E. Kwan, J. L. Watts, A. L. Lawrenson, and G. J. Hermann (2007)
Mol. Biol. Cell 18, 995-1008
   Abstract »    Full Text »    PDF »
Novel Munc13-4 mutations in children and young adult patients with haemophagocytic lymphohistiocytosis.
A Santoro, S Cannella, G Bossi, F Gallo, A Trizzino, D Pende, F Dieli, G Bruno, J C Stinchcombe, C Micalizzi, et al. (2006)
J. Med. Genet. 43, 953-960
   Abstract »    Full Text »    PDF »
Rab38 and Rab32 control post-Golgi trafficking of melanogenic enzymes.
C. Wasmeier, M. Romao, L. Plowright, D. C. Bennett, G. Raposo, and M. C. Seabra (2006)
J. Cell Biol. 175, 271-281
   Abstract »    Full Text »    PDF »
Identification and Validation of Mannose 6-Phosphate Glycoproteins in Human Plasma Reveal a Wide Range of Lysosomal and Non-lysosomal Proteins.
D. E. Sleat, Y. Wang, I. Sohar, H. Lackland, Y. Li, H. Li, H. Zheng, and P. Lobel (2006)
Mol. Cell. Proteomics 5, 1942-1956
   Abstract »    Full Text »    PDF »
A Scan for Signatures of Positive Selection in Candidate Loci for Skin Pigmentation in Humans.
N. Izagirre, I. Garcia, C. Junquera, C. de la Rua, and S. Alonso (2006)
Mol. Biol. Evol. 23, 1697-1706
   Abstract »    Full Text »    PDF »
Exosomes: a common pathway for a specialized function..
G. van Niel, I. Porto-Carreiro, S. Simoes, and G. Raposo (2006)
J. Biochem. 140, 13-21
   Abstract »    Full Text »    PDF »
Lethal hemophagocytic lymphohistiocytosis in Hermansky-Pudlak syndrome type II.
A. Enders, B. Zieger, K. Schwarz, A. Yoshimi, C. Speckmann, E.-M. Knoepfle, U. Kontny, C. Muller, A. Nurden, J. Rohr, et al. (2006)
Blood 108, 81-87
   Abstract »    Full Text »    PDF »
Innate immunity defects in Hermansky-Pudlak type 2 syndrome.
S. Fontana, S. Parolini, W. Vermi, S. Booth, F. Gallo, M. Donini, M. Benassi, F. Gentili, D. Ferrari, L. D. Notarangelo, et al. (2006)
Blood 107, 4857-4864
   Abstract »    Full Text »    PDF »
Identification of novel th2-associated genes in T memory responses to allergens..
A. Bosco, K. L. McKenna, C. J. Devitt, M. J. Firth, P. D. Sly, and P. G. Holt (2006)
J. Immunol. 176, 4766-4777
   Abstract »    Full Text »    PDF »
The Guanine Nucleotide Exchange Factor CNrasGEF Regulates Melanogenesis and Cell Survival in Melanoma Cells.
E. M. Amsen, N. Pham, Y. Pak, and D. Rotin (2006)
J. Biol. Chem. 281, 121-128
   Abstract »    Full Text »    PDF »
Functions of Adaptor Protein (AP)-3 and AP-1 in Tyrosinase Sorting from Endosomes to Melanosomes.
A. C. Theos, D. Tenza, J. A. Martina, I. Hurbain, A. A. Peden, E. V. Sviderskaya, A. Stewart, M. S. Robinson, D. C. Bennett, D. F. Cutler, et al. (2005)
Mol. Biol. Cell 16, 5356-5372
   Abstract »    Full Text »    PDF »
Inefficient Cell Spreading and Cytoskeletal Polarization by CD4+CD8+ Thymocytes: Regulation by the Thymic Environment.
E. Hailman and P. M. Allen (2005)
J. Immunol. 175, 4847-4857
   Abstract »    Full Text »    PDF »
Drosophila Vps16A is required for trafficking to lysosomes and biogenesis of pigment granules.
S. Pulipparacharuvil, M. A. Akbar, S. Ray, E. A. Sevrioukov, A. S. Haberman, J. Rohrer, and H. Kramer (2005)
J. Cell Sci. 118, 3663-3673
   Abstract »    Full Text »    PDF »
Hereditary Hormone Excess: Genes, Molecular Pathways, and Syndromes.
S. J. Marx and W. F. Simonds (2005)
Endocr. Rev. 26, 615-661
   Abstract »    Full Text »    PDF »
C. elegans sperm bud vesicles to deliver a meiotic maturation signal to distant oocytes.
M. Kosinski, K. McDonald, J. Schwartz, I. Yamamoto, and D. Greenstein (2005)
Development 132, 3357-3369
   Abstract »    Full Text »    PDF »
Genetic Analysis of Lysosomal Trafficking in Caenorhabditis elegans.
G. J. Hermann, L. K. Schroeder, C. A. Hieb, A. M. Kershner, B. M. Rabbitts, P. Fonarev, B. D. Grant, and J. R. Priess (2005)
Mol. Biol. Cell 16, 3273-3288
   Abstract »    Full Text »    PDF »
Macroarray analysis of coelomocyte gene expression in response to LPS in the sea urchin. Identification of unexpected immune diversity in an invertebrate.
S. V. Nair, H. Del Valle, P. S. Gross, D. P. Terwilliger, and L. C. Smith (2005)
Physiol Genomics 22, 33-47
   Abstract »    Full Text »    PDF »
Linkage of familial hemophagocytic lymphohistiocytosis (FHL) type-4 to chromosome 6q24 and identification of mutations in syntaxin 11.
U. zur Stadt, S. Schmidt, B. Kasper, K. Beutel, A. S. Diler, J.-I. Henter, H. Kabisch, R. Schneppenheim, P. Nurnberg, G. Janka, et al. (2005)
Hum. Mol. Genet. 14, 827-834
   Abstract »    Full Text »    PDF »
Versatile Role of Rab27 in Membrane Trafficking: Focus on the Rab27 Effector Families.
M. Fukuda (2005)
J. Biochem. 137, 9-16
   Abstract »    Full Text »    PDF »
Familial and Acquired Hemophagocytic Lymphohistiocytosis.
G. Janka and U. zur Stadt (2005)
Hematology 2005, 82-88
   Abstract »    Full Text »    PDF »


To Advertise     Find Products

Science. ISSN 0036-8075 (print), 1095-9203 (online)