When cell biology meets development: endocytic regulation of signaling pathways

  1. Elaine S. Seto1,5,
  2. Hugo J. Bellen1,2,3,4,6, and
  3. Thomas E. Lloyd2,5
  1. 1Program in Developmental Biology, 2Department of Molecular and Cellular Biology, 3Howard Hughes Medical Institute, and 4Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas 77030, USA

This extract was created in the absence of an abstract.

Recent advances in membrane trafficking and signal transduction, once considered unrelated disciplines of cell biology, suggest that these fields are intimately intertwined. The sorting of signals and their receptors to different membrane-bound compartments plays a critical role in modulating the level and localization of signaling during development. Moreover, signaling pathways may interact with and regulate components of the membrane trafficking machinery. The relationship between these two fields is likely to be an area of intense future research as the interface of membrane trafficking and intercellular signaling appears to play an important role in development, physiology, and disease.

Recent work performed in many different systems has implicated nearly every membrane trafficking event as a potential site for the regulation of signaling pathways (Di Fiore and De Camilli 2001). The temporal and spatial delivery of signals and their receptors to different intracellular membrane-bound compartments is tightly regulated during development. Traditionally, endocytosis has been considered a mechanism to down-regulate receptors, desensitizing cells to signaling molecules. However, recent work has shown that endocytosis regulates signaling through multiple mechanisms. First, in receptor tyrosine kinase (RTK) signaling, endocytosis may increase signaling by associating internalized receptors with signaling targets localized to endosomes and decrease signaling by sorting receptors to the lysosome for degradation. Second, endocytosis may serve to regulate the distribution of signaling molecules. In the case of Wingless and transforming growth factor β (TGF-β)/Decapentaplegic (DPP), a form of endocytosis called transcytosis has been proposed to form morphogen gradients, and gradients can be shaped by controlling the recycling and degradation of internalized signaling molecules. Finally, internalization may be required to activate receptors, as is the case of Notch signaling. These proposed roles for endocytosis are likely to be important in the regulation of many signaling pathways during development.

Here we will review the process of endocytosis as …

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