The dependence receptor family, Dr. Jekyll and Mr. Hyde

P75(ntr) (the common neurotrophin receptor), the androgen receptor, RET (REarranged during Transfection), DCC (Deleted in Colorectal Cancer) and UNC5H are members of the growing list of dependence receptors. Such receptors, by inducing apoptosis when expressed in setting where their ligands are unavailable, create a cellular state of dependence for their ligands. Of interest all this receptors are involved in cancer progression, nervous system associated diseases and/or development of the nervous system. As an example, DCC encodes for a potential tumor suppressor but in the same time is a key receptor in mediating axon guidance induced by the cue netrin-1. These receptors show two distinct forms of signal transduction depending on their respective ligand availability: in the presence of their ligands, they transduce a signal for either proliferation, differentiation or neuronal migration; however, they are not inactive in the absence of their ligands, but rather induce an active signal for cell death. This new concept is reviewed here enlightening the molecular mechanisms of these receptors and their potential relevance in vivo in the development of the nervous system and in the control of tumorigenesis.