citation_keywords: Ca2+ channel interaction; channel clustering; active zone protein; Hair cells; ribbon synapse; Exocytosis; Hearing
citation_publication_date: 2017/06/08
citation_title: Rab Interacting Molecules 2 and 3 Directly Interact with the Pore-Forming CaV1.3 Ca2+ Channel Subunit and Promote Its Membrane Expression
citation_author_institution: Institute for Auditory Neuroscience and InnerEarLab, University Medical Center Göttingen, Göttingen, Germany
Description: Rab interacting molecules (RIMs) are multi-domain proteins that positively regulate the number of Ca2+ channels at the presynaptic active zone (AZ). Several molecular mechanisms have been demonstrated for RIM-binding to components of the presynaptic Ca2+ channel complex, the key signaling element at the AZ. Here, we report an interaction of the C2B domain of RIM2? and RIM3? with the C-terminus of the pore-forming ??subunit of CaV1.3 channels (CaV1.3?1), which mediate stimulus-secretion coupling at the ribbon synapses of cochlear inner hair cells (IHCs). Co-expressing full-length RIM2? with a Ca2+ channel complex closely resembling that of IHCs (CaV1.3?1-CaVß2a) in HEK293 cells doubled the Ca2+-current and shifted the voltage-dependence of Ca2+ channel activation by approximately +3 mV. Co-expression of the short RIM isoform RIM3? increased the CaV1.3?1-CaVß2a-mediated Ca2+-influx in HEK293 cells, but disruption of RIM3? in mice left Ca2+-influx in IHCs and hearing intact. In conclusion, we propose that RIM2? and RIM3? directly interact with the C-terminus of the pore-forming subunit of CaV1.3 Ca2+ channels and positively regulate their plasma membrane expression in HEK293 cells.
Keywords: Ca2+ channel interaction, channel clustering, active zone protein, Hair cells, ribbon synapse, Exocytosis, Hearing
citation_publisher: Frontiers
citation_journal_title: Frontiers in Cellular Neuroscience
description: Rab interacting molecules (RIMs) are multi-domain proteins that positively regulate the number of Ca2+ channels at the presynaptic active zone (AZ). Several molecular mechanisms have been demonstrated for RIM-binding to components of the presynaptic Ca2+ channel complex, the key signaling element at the AZ. Here, we report an interaction of the C2B domain of RIM2? and RIM3? with the C-terminus of the pore-forming ??subunit of CaV1.3 channels (CaV1.3?1), which mediate stimulus-secretion coupling at the ribbon synapses of cochlear inner hair cells (IHCs). Co-expressing full-length RIM2? with a Ca2+ channel complex closely resembling that of IHCs (CaV1.3?1-CaVß2a) in HEK293 cells doubled the Ca2+-current and shifted the voltage-dependence of Ca2+ channel activation by approximately +3 mV. Co-expression of the short RIM isoform RIM3? increased the CaV1.3?1-CaVß2a-mediated Ca2+-influx in HEK293 cells, but disruption of RIM3? in mice left Ca2+-influx in IHCs and hearing intact. In conclusion, we propose that RIM2? and RIM3? directly interact with the C-terminus of the pore-forming subunit of CaV1.3 Ca2+ channels and positively regulate their plasma membrane expression in HEK293 cells.
citation_date: 2017
title: Frontiers | Rab Interacting Molecules 2 and 3 Directly Interact with the Pore-Forming CaV1.3 Ca2+ Channel Subunit and Promote Its Membrane Expression | Frontiers in Cellular Neuroscience
citation_online_date: 2017/05/23
citation_author_email: 
citation_issn: 1662-5102
dc:title: Frontiers | Rab Interacting Molecules 2 and 3 Directly Interact with the Pore-Forming CaV1.3 Ca2+ Channel Subunit and Promote Its Membrane Expression | Frontiers in Cellular Neuroscience
citation_language: English
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citation_journal_abbrev: Front. Cell. Neurosci.
citation_abstract: Rab interacting molecules (RIMs) are multi-domain proteins that positively regulate the number of Ca2+ channels at the presynaptic active zone (AZ). Several molecular mechanisms have been demonstrated for RIM-binding to components of the presynaptic Ca2+ channel complex, the key signaling element at the AZ. Here, we report an interaction of the C2B domain of RIM2? and RIM3? with the C-terminus of the pore-forming ??subunit of CaV1.3 channels (CaV1.3?1), which mediate stimulus-secretion coupling at the ribbon synapses of cochlear inner hair cells (IHCs). Co-expressing full-length RIM2? with a Ca2+ channel complex closely resembling that of IHCs (CaV1.3?1-CaVß2a) in HEK293 cells doubled the Ca2+-current and shifted the voltage-dependence of Ca2+ channel activation by approximately +3 mV. Co-expression of the short RIM isoform RIM3? increased the CaV1.3?1-CaVß2a-mediated Ca2+-influx in HEK293 cells, but disruption of RIM3? in mice left Ca2+-influx in IHCs and hearing intact. In conclusion, we propose that RIM2? and RIM3? directly interact with the C-terminus of the pore-forming subunit of CaV1.3 Ca2+ channels and positively regulate their plasma membrane expression in HEK293 cells.
citation_author: Picher, Maria M.
Title: Rab Interacting Molecules 2 and 3 Directly Interact with the Pore-Forming CaV1.3 Ca2+ Channel Subunit and Promote Its Membrane Expression
citation_pages: 160
image_src: http://www.frontiersin.org/files/MyHome%20Article%20Library/264619/264619_Thumb_400.jpg
url: http://journal.frontiersin.org/article/10.3389/fncel.2017.00160/full
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citation_doi: 10.3389/fncel.2017.00160
dc.identifier: doi:10.3389/fncel.2017.00160
citation_volume: 11
Content-Language: en