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Endosomes by Ivan Dikic

By Ivan Dikic

Endosomes are a heterogeneous inhabitants of endocytic vesicles and tubules that experience captivated the curiosity of biologists for a few years, partially as a result of their very important mobile capabilities and in part because of their fascinating nature and dynamics. Endosomes characterize a desirable interconnected community of millions of vesicles that shipping a number of cargoes, commonly proteins and lipids, to far-off mobile locations. How endosomes functionality, what co-ordinates the molecular determinants at each one step in their dynamic existence cycle and what their organic and scientific relevance is, are one of the questions addressed during this book.

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Rab9 domains, regulating transport between late endosomes and trans-Golgi network (TGN), are enriched in specific cargo (cation-independent mannose 6-phosphate receptors, CI-MPR) and contain Rab9 effector TIP47. In contrast, Rab7 domains are postulated to mediate the transport of cargo from early endosomes towards degradation in lysosomes. Thus, two different trafficking routes through late endosomes appear to be spatially separated and regulated by distinct Rab domains. Overall, the endosomal compartments can therefore be considered as a mosaic of various domains occupied by Rab proteins and their effectors.

Mammalian cell morphology and endocytic membrane homeostasis require enzymatically active phosphoinositide 5-kinase PIKfyve. J Biol C h e m 2 0 0 1 ; 276(28):26l4l-7. 22. Friant S, Pecheur EI, Eugster A et al. Ent3p is a PtdIns(3,5)P2 effector required for protein sorting to the multivesicular body. Dev Cell 2003; 5(3):499-511. 23. Eugster A, Pecheur EI, Michel F et al. E n t 5 p is required w i t h E n t 3 p and V p s 2 7 p for u b i q u i t i n - d e p e n d e n t p r o t e i n sorting i n t o the multivesicular b o d y .

Each Rab protein is characterized by a specific and restricted intracellular distribution. Several Rabs have been localized to endosomal compartments and/or implicated in the regulation of various endocytic events. ^^ However, only a few of diese proteins have been characterized in more detail. '^^'^^ Due to their specific localization to various membrane compartments throughout the cell, Rab proteins have been long recognized as organelle markers and their role as rate-limiting regulators of transport is well established.

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