Emerging roles of collapsin response mediator proteins (CRMPs) as regulators of voltage-gated calcium channels and synaptic transmission

Commun Integr Biol. 2010 Mar;3(2):172-5. doi: 10.4161/cib.3.2.10620.


Presynaptic N-type voltage-gated Ca(2+) channels (Cav2.2) form part of an extensive macromolecular complex in the presynaptic terminal. Regulation of Cav2.2 is achieved via protein-protein interactions within the terminal and can directly impact transmitter release which is dependent on Ca(2+) influx via these Cav2.2. We recently identified a novel Cav2.2 interacting partner-the collapsin response mediator protein (CRMP).1 CRMPs are a family of five proteins implicated in signal transduction of neurite outgrowth and axonal guidance. We showed that CRMP-2, a wellstudied member of this family, interacted with Cav2.2 via direct binding to cytoplasmic loops of Cav2.2. Depolarization enhanced the interaction. Further studies revealed that CRMP-2 facilitated an increase in Cav2.2 current density by inserting more Cav2.2 at the cell surface. As a consequence of CRMP-2-mediated increase in Ca(2+) influx, release of the excitatory neurotransmitter glutamate was also increased. CRMP-2 localized to synapses where, surprisingly, its overexpression increased synapse size. We hypothesize that the CRMP-2-calcium channel interaction represents a novel mechanism for modulation of Ca(2+) influx into nerve terminals and, hence, of synaptic strength. In this addendum, we further discuss the significance of this study and the possible implications to the field.

Keywords: CRMP-2; Cav2.2; axonal outgrowth; growth cone; presynaptic calcium channels; surface trafficking; synaptic transmission.