Michael S Marks

..Furthermore, they implicate an unusual clathrin-coated endosomal compartment as a site from which proteins destined for premelanosomes and lysosomes are sorted...

..By using a similar chimeric protein approach to target endogenous proteins to distinct compartments, we hope to address the role of processing events in each compartment in the generation of MHC class II ligands...

..The recent characterization of genes defective in these diseases has reinvigorated interest in the melanosome as a model system for understanding the molecular mechanisms that underlie intracellular membrane dynamics...

..Our studies on melanosome biogenesis are providing new ways of thinking about antigen-processing compartments and the mechanisms regulating presentation of tumor-associated antigens...

..Our data delineate a novel pathway for Tyrp1 trafficking and illustrate a requirement for ESCRT-I function in controlling protein sorting from vacuolar endosomes to the limiting membrane of a lysosome-related organelle...

..These data have important implications for the site and mechanism of fibril formation...

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..These results establish an Hrs- and perhaps ESCRT-independent pathway of ILV sorting by lumenal determinants and a requirement for ILV sorting in fibril formation...

..These data reveal a dual sorting defect in a natural mutant of Pmel17 and support a requirement of endocytic trafficking in Pmel17 fibril formation...

..We speculate that PMEL mutations can model the conversion between physiological and pathological amyloid...

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..The expression of an alternatively spliced product may furthermore affect the cohort of peptides generated for recognition of melanoma cells by tumor-directed T lymphocytes...

..We conclude that OCA2 is targeted to and functions within melanosomes but that residence within melanosomes may be regulated by secondary or alternative targeting to lysosomes...

..These data define the structural core of Pmel17 amyloid, imply that the RPT domain plays a regulatory role in timing amyloid conversion, and suggest that fibril formation might be physically linked with multivesicular body sorting...

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..As such, we will refer to the protein in this review simply as pre-melanosomal protein (Pmel). This review will summarize the structural and functional aspects of Pmel and its role in melanosome biogenesis...

..These data reveal a novel pathway by which uPA is rapidly translocated to the nucleus where it might participate in regulating gene expression...

..Collectively, these studies suggest that MREG is required for lysosome maturation and support a role for MREG in intracellular trafficking...

..These data demonstrate that tGolgin-1 functions in Golgi positioning indirectly, probably by regulating retrograde movement of cargo required for recruitment or activation of dynein-dynactin complexes on newly formed Golgi elements...

..These results demonstrate a novel mechanism by which tumors may evade CD4(+) T cell-dependent immune responses through expression of a TAA...

..Wasmeier et al. (this issue, p. 271) reveal a redundant role for two tissue-specific Rab proteins in regulating transport to a tissue-specific lysosome-related organelle, the melanosome...

..These studies reveal a previously unappreciated link of Erk signaling to organelle dynamics and endosomal trafficking...

..Like the pathologic process of amyloidogenesis, the formation of other tissue-specific organelle structures may be similarly dependent on proteolytic activation of physiological fibrillogenic substrates...

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..The similar requirements for localization of GRIP domains from yeast, mouse, and human when expressed in yeast, and the presence of Arl1p and Arl3p homologs in these species, suggest that this is an evolutionarily conserved mechanism...

..This expression pattern suggests that tGolgin-1 may play a role in specialized transport processes associated with maturation and/or differentiation of oligodendrocyte precursors...

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..These findings support the idea that BLOC-1 and -2 represent hitherto unknown components of the endosomal protein trafficking machinery...

..Current research reveals how the products of these genes cooperate to generate LROs and how these otherwise diverse organelles are related by the mechanisms through which they form...

..Further dissection of the melanosomal system will likely shed light not only on the biogenesis of lysosome-related organelles but also on general aspects of vesicular transport in the endosomal system...

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..Moreover, genetic disorders that affect the biogenesis of melanosomes and other lysosome-related organelles have shed light onto the molecular machinery that controls specialized endosomal sorting events...

..In this review we highlight adaptations and malfunction of the endosomal/lysosomal system in normal and pathological situations with special focus on MHC class II compartments in antigen presenting cells and melanosomes in pigment cells...

..3. To test the hypothesis that HPS-associated gene products function in protein sorting at the stage I melanosome. ..

..This proposal tests the hypothesis that Hermansky Pudlak Syndrome results from iron and copper dysregulation in the affected cell types. ..

..PmeU 7 forms amyloid-like fibers within pigment cells. By defining the mechanism, we may uncover potential cures for albinism, hyperpigmented lesions, and/or neurodegenerative amyloid diseases like Alzheimer's. ..

..PmeU 7 forms amyloid-like fibers within pigment cells. By defining the mechanism, we may uncover potential cures for albinism, hyperpigmented lesions, and/or neurodegenerative amyloid diseases like Alzheimer's. ..

..PmeU 7 forms amyloid-like fibers within pigment cells. By defining the mechanism, we may uncover potential cures for albinism, hyperpigmented lesions, and/or neurodegenerative amyloid diseases like Alzheimer's. ..

..PmeU 7 forms amyloid-like fibers within pigment cells. By defining the mechanism, we may uncover potential cures for albinism, hyperpigmented lesions, and/or neurodegenerative amyloid diseases like Alzheimer's. ..

..3. Determine the range of Nmb localization and splice variation in eye tissue of disease-free donors and pigmentary glaucoma patients. ..

..3. Determine the molecular form of Pmel17 found within striation- containing premelanosomes. 4. Determine whether additional premelanosomal components contribute to striation formation. ..

..The effect of altering the protein sorting and/or retention properties of tyrosinase and gp100 on recognition by specific T cell clones will be determined. ..

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