Figure 2.
Signaling dynamics of PTHR on the early endosome. (a) We have recently shown that complexes of β-arrestin 1 (red) and PTHR (green) internalize to a compartment of the early endosome that is labeled red-green in a 3D reconstruction of early endosomes visualized with a spectral confocal microscope (top). A second compartment labeled with the sorting complex retromer (blue) is labeled blue-green. Arrestin and retromer do not colocalize, indicating that the two proteins localize in distinct compartments of the endosome, most likely the bulk domain (arrestin) and a domain dedicated to endosome-to-Golgi retrograde traffic (retromer). (b) Persistent complexes of PTHR-arrestin generate cAMP (yellow) from endosomal membranes. However, after arrestin-receptor decoupling, PTHR is free to bind retromer and sort to a compartment that does not support cAMP generation. Retromer-bound inactive PTHR then sorts to the trans-Golgi network before recycling to the plasma membrane. Adapted from (26).