First published online April 3, 2008
Journal of Cell Science 121, 803e (2008)
© The Company of Biologists Limited
Insulin signalling: directing traffic
In muscle cells and adipocytes, the insulin-responsive aminopeptidase IRAP is trafficked to the insulin-responsive compartment (IRC) following its biosynthesis. When insulin is detected, IRAP translocates to the plasma membrane, and is later endocytosed and recycled to the IRC. However, little is known about how the insulin-dependent redistribution of IRAP is controlled. Here, Robert T. Watson and Jeffrey E. Pessin (p. 1243) analyse the molecular determinants of IRAP localisation in adipocytes. The authors show that a dileucine motif at positions 76 and 77 of IRAP – which is required for targeting IRAP to the IRC after its synthesis – is not required for trafficking from the plasma membrane to the IRC. Similarly, the clathrin adaptor protein GGA directs the post-synthesis trafficking of IRAP from the Golgi to the IRC, but does not affect its subsequent translocation to the plasma membrane. The authors go on to show that syntaxin 6, a SNARE protein, is required for the re-entry of IRAP to the IRC following endocytosis. Thus, the different phases of the intracellular trafficking of IRAP are controlled by distinct proteins and by sorting motifs within IRAP itself.
Related articles in JCS:
- Recycling of IRAP from the plasma membrane back to the insulin-responsive compartment requires the Q-SNARE syntaxin 6 but not the GGA clathrin adaptors
- Robert T. Watson and Jeffrey E. Pessin
JCS 2008 121: 1243-1251.
[Abstract]
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