RapGAPs in brain: multipurpose players in neuronal Rap signalling

Small Rap guanosine-tri-phosphate (GTP)ases are crucially involved in many cellular processes, including cell proliferation, differentiation, survival, adhesion and movement. In line, it has been shown that Rap signalling is involved in various aspects of neuronal differentiation, like the establishment of neuronal polarity or axonal growth cone movement. Rap GTPases can be activated by a wide variety of external stimuli, and this is mediated by specific guanine nucleotide exchange factors (RapGEFs). Inactivation of RapGTP can be achieved with the aid of specific GTPase-activating proteins (RapGAPs). In the brain, the most prominent RapGAPs are Rap1GAP and those of the spine-associated RapGAP (SPAR) family. This latter family consists of three members (SPAR1-3), from which two of them, namely SPAR1 and 2, have been investigated in more detail. As such, the localization of RapGAPs is crucially important in regulating Rap signalling at various sites in the cell and, for both SPAR1 and 2, enrichment at synaptic sites has been demonstrated. In recent years particularly the role of SPAR1 in shaping dendritic spine morphology has attracted considerable interest. In this review we will summarize the described actions of different RapGAPs expressed in the brain, and we will focus in particular on the SPAR family members.