A5008176464- melanin and skin pigmentation
- RNA regulation and disease
- Cellular transport and secretion
- Biochemical Analysis and Sensing Techniques
- Retinal Development and Disorders
- Platelet Disorders and Treatments
- Mast cells and histamine
- Erythrocyte Function and Pathophysiology
- Proteoglycans and glycosaminoglycans research
- Skin Protection and Aging
- Hematopoietic Stem Cell Transplantation
- Multiple Myeloma Research and Treatments
- Myeloproliferative Neoplasms: Diagnosis and Treatment
- Atherosclerosis and Cardiovascular Diseases
- Barrier Structure and Function Studies
- Extracellular vesicles in disease
- Microbial Metabolism and Applications
- Periodontal Regeneration and Treatments
- Plant Gene Expression Analysis
- Glycosylation and Glycoproteins Research
- Reproductive Biology and Fertility
- CRISPR and Genetic Engineering
- Cell Adhesion Molecules Research
- Dyeing and Modifying Textile Fibers
- Cutaneous Melanoma Detection and Management
Children's Hospital of Philadelphia
2014-2023
University of Pennsylvania
2006-2023
Czech Academy of Sciences, Institute of Physiology
2014
Melanosomes are tissue-specific organelles within which melanin is synthesized and stored. The melanocyte-specific glycoprotein Pmel17 enriched in the lumen of premelanosomes, where it associates with characteristic striations unknown composition upon deposited. However, as an integral membrane protein. To clarify its physical linkage to we analyzed posttranslational processing human pigmented transfected nonpigmented cells. We show that cleaved a post-Golgi compartment into two...
Lysosome-related organelles are cell type–specific intracellular compartments with distinct morphologies and functions. The molecular mechanisms governing the formation of their unique structural features not known. Melanosomes precursors lysosome-related that characterized morphologically by intralumenal fibrous striations upon which melanins polymerized. integral membrane protein Pmel17 is a component fibrils can nucleate in absence other pigment cell–specific proteins. Here, we show...
Pmel17 is a pigment cell-specific integral membrane protein that participates in the formation of intralumenal fibrils upon which melanins are deposited melanosomes. The cytoplasmic domain truncated by mouse silver mutation, associated with coat hypopigmentation certain strain backgrounds. Here, we show truncation interferes at least two steps intracellular transport, resulting defects melanosome biogenesis. Human engineered found mutant (hPmel17si) inefficiently exported from endoplasmic...
Melanin pigments are synthesized within specialized organelles called melanosomes and polymerize on intraluminal fibrils that form melanosome precursors. The consist of proteolytic fragments derived from Pmel17, a pigment cell-specific integral membrane protein. intracellular pathways by which Pmel17 accesses precursors the identity derivatives fibrillar have been matter debate. We show here antibodies detect recognize only luminal products proprotein convertase cleavage not remaining linked...
Oculocutaneous albinism type 2 is caused by defects in the gene OCA2, encoding a pigment cell-specific, 12-transmembrane domain protein with homology to ion permeases. The function of OCA2 remains unknown, and its subcellular localization under debate. Here, we show that endogenous melanocytic cells rapidly exits endoplasmic reticulum (ER) thus does not behave as resident ER protein. Consistently, exogenously expressed localizes within melanocytes melanosomes, and, like other melanosomal...
Melanoregulin (MREG), the product of Mreg(dsu) gene, is a small highly charged protein, hypothesized to play role in organelle biogenesis due its effect on pigmentation dilute, ashen, and leaden mutant mice. Here we provide evidence that MREG required lysosome-dependent phagosome degradation. In Mreg(-/-) mouse, show loss function results accumulation delayed degradation engulfed material. Over time, mouse retinal pigment epithelial cells accumulate lipofuscin component, A2E. MREG-deficient...
Melanosomes are lysosome‐related organelles that coexist with lysosomes within melanocytes. The pathways by which melanosomal proteins diverted from endocytic toward melanosomes incompletely defined. In melanocytes mouse models of Hermansky‐Pudlak syndrome lack BLOC‐1, such as tyrosinase‐related protein 1 (Tyrp1) accumulate in early endosomes. Whether this accumulation represents an anomalous pathway or arrested normal intermediate melanosome trafficking is not clear. Here, we show endosomes...
tGolgin-1 (golgin-245, trans golgi p230) and golgin-97 are members of a family peripheral membrane proteins unknown function that localize to the Golgi network (TGN) through conserved C-terminal GRIP domain. We have probed for protein by assessing consequences overexpressing isolated domains. By semi-quantitative immunofluorescence microscopy we found high level expression epitope-tagged, domain-containing fragments or specifically altered characteristic pericentriolar distribution TGN...
Membrane transport carriers fuse with target membranes through engagement of cognate vSNAREs and tSNAREs on each membrane. How are sorted into is incompletely understood. Here we show that VAMP7, the vSNARE for fusing endosome-derived tubular maturing melanosomes in melanocytes, complex tSNARE component STX13. Sorting requires either recognition VAMP7 by AP-3δ subunit AP-3 or STX13 pallidin BLOC-1, but not both. Consequently, melanocytes expressing both variants cannot bind their respective...
Proteolytic fragments of the pigment cell-specific glycoprotein, PMEL, form amyloid fibrillar matrix underlying melanins in melanosomes. The fibrils within multivesicular endosomes to which PMEL is selectively sorted and that serve as melanosome precursors. GPNMB a tissue-restricted glycoprotein with substantial sequence homology but no known function, was proposed localize non-fibrillar domains distinct subcompartments melanocytes. Here we confirm localizes compartments from PMEL-containing...
The biochemical pathway regulating the synthesis of yellow/red pheomelanin is less well characterized than black/brown eumelanin. Inhibitor gold (IG phenotype) a plumage colour variant in chicken that provides an opportunity to further explore this since recessive allele ( IG ) at locus associated with defect production pheomelanin. IG/IG homozygotes display marked dilution red pigmentation, whilst black pigmentation (eumelanin) only slightly affected. Here we show 2-base pair insertion...
Hermansky‐Pudlak syndrome (HPS) is a group of rare genetic diseases characterized by oculocutaneous albinism and bleeding diathesis, often associated with lung fibrosis. The symptoms HPS reflect defects in membrane transport processes required to generate tissue‐specific lysosome‐related organelles (LROs), such as melanosomes pigment cells, lamellar bodies (LB) type 2 alveolar epithelial cells (AT2) dense granules platelets. Although the that are defective shared among distinct...
SUMMARY Color variation is a frequent evolutionary substrate for camouflage in small mammals but the underlying genetics and forces that drive color natural populations of large are mostly unexplained. The American black bear, Ursus americanus , exhibits range colors including cinnamon morph which has similar to brown U. arctos found at high frequency southwest. Reflectance chemical melanin measurements showed little distinction between individuals. We used genome-wide association hair as...