Expanding our current hypothesis

Our current working hypothesis is that sICD, the intracellular cleaved fraction of FGFR3 is involved in regulating at least some of the FGFR3 functions in bone growth and development. We believe it is doing so in part through interactions within the nucleus and possibly through interactions with DNA.  But there are other aspects involved in FGFR3 regulation of bone growth that are essential and will also need to be focused. Let us take a look at two such ideas -

1.      Subcellular localization and nuclear translocation – To function in the nucleus, the sICD first needs to be transported to the nucleus. This transport to the nucleus is likely to be a regulated process.  There are two ways that the sICD could get into the nucleus. First, it has within its sequence a nuclear translocation signal that allows it to go to the nucleus, or second, it is aided by another protein that delivers it to the nucleus. We are yet to identify the mechanism that lets sICD get into the nucleus.

2.      That brings us to our next question. Does sICD interact with other proteins? Protein-protein interactions are known to be important for cellular regulation. Proteins interact with other proteins to form a complex cellular network, and these networks are responsible to carry out cellular functions. Within these networks, protein interactions relay signals that lead to changes in gene expression. Identifying interacting partners can therefor be very useful and can give us some hint about possible  protein functions. Identifying sICD interacting proteins will therefore be important in identifying  possible genes that may be regulated by sICD. Some of the cellular pathways that involve FGFR3 have been characterized by others and will be useful as a starting point.

We are in the process of addressing some of these ideas. We will take a look at the techniques and experiments used to answer these questions.