Regulating FGFR3 degradation

Down regulation of receptor signaling often involves internalization of the receptor followed by its degradation.  Fewer active receptors found on the cell surface mean lesser capacity for signal. Reduced number of receptors on the surface also affects the duration of a particular signal. Accordingly, internalization of FGFR3 will reduce its signaling capacity on the surface and provide an important regulatory mechanism for decreasing FGFR3 signaling. Internalization of receptor (by a process called endocytosis) can take place through one or more pathways as shown in the figure below. 

We have previously shown that FGFR3 can be internalized in a clathrin/dynamin-dependent manner and this is required for receptor cleavage to occur that generates the soluble intracellular piece (sICD) (Degnin et al, 2011). Others have reported that FGFR3 may be internalized by both clathrin-dependent and clathrin-independent mechanisms. The mechanism of FGFR3 degradation has not been clearly delineated. We have evidence that FGFR3 forms a complex with proteins, called chaperones that help keep FGFR3 stable. Upon dissociation from the chaperone complex, FGFR3 gets processed and is degraded. The chaperone complexes seem to be important in maintaining stable FGFR3 and therefore also become important targets that affect FGFR3 degradation.