| First Author | Picher MM | Year | 2017 |
| Journal | Front Cell Neurosci | Volume | 11 |
| Pages | 160 | PubMed ID | 28642685 |
| Mgi Jnum | J:253590 | Mgi Id | MGI:6109296 |
| Doi | 10.3389/fncel.2017.00160 | Citation | Picher MM, et al. (2017) Rab Interacting Molecules 2 and 3 Directly Interact with the Pore-Forming CaV1.3 Ca(2+) Channel Subunit and Promote Its Membrane Expression. Front Cell Neurosci 11:160 |
| abstractText | Rab interacting molecules (RIMs) are multi-domain proteins that positively regulate the number of Ca(2+) channels at the presynaptic active zone (AZ). Several molecular mechanisms have been demonstrated for RIM-binding to components of the presynaptic Ca(2+) channel complex, the key signaling element at the AZ. Here, we report an interaction of the C2B domain of RIM2alpha and RIM3gamma with the C-terminus of the pore-forming alpha-subunit of CaV1.3 channels (CaV1.3alpha1), which mediate stimulus-secretion coupling at the ribbon synapses of cochlear inner hair cells (IHCs). Co-expressing full-length RIM2alpha with a Ca(2+) channel complex closely resembling that of IHCs (CaV1.3alpha1-CaVss2a) in HEK293 cells doubled the Ca(2+)-current and shifted the voltage-dependence of Ca(2+) channel activation by approximately +3 mV. Co-expression of the short RIM isoform RIM3gamma increased the CaV1.3alpha1-CaVss2a-mediated Ca(2+)-influx in HEK293 cells, but disruption of RIM3gamma in mice left Ca(2+)-influx in IHCs and hearing intact. In conclusion, we propose that RIM2alpha and RIM3gamma directly interact with the C-terminus of the pore-forming subunit of CaV1.3 Ca(2+) channels and positively regulate their plasma membrane expression in HEK293 cells. |
