Protein trafficking inherited disorders

Several different mutant genes in humans and mice were identified on the basis of reduced pigmentation associated with defects of multiple cytoplasmic organelles melanosomes, lysosomes and platelet granules. Pigmentary changes involve the skin, hair and eyes, whereas abnormal platelets lead to bleeding disturbance and abnormal lysosome structure or function affects mostly cells of the hematopoietic lineage. Affected organelles have the characteristics of secretory lysosomes which utilize specialized mechanisms for sorting and secretion, differing from those found in conventional secretory cells. Recent findings show that several of the molecular defects accounting for these diseases directly affect components in the pathway of organelle-specific protein trafficking. Their analysis provides new Insights into the various pathways used by these cells for protein secretion and point out a key role of protein trafficking in the maintenance of Immune homeostasis.