Differential Distribution of Retinal Ca2+/Calmodulin-Dependent Kinase II (CaMKII) Isoforms Indicates CaMKII-β and -δ as Specific Elements of Electrical Synapses Made of Connexin36 (Cx36)
AII amacrine cells are essential interneurons of the primary rod pathway and transmit rod-driven signals to ON cone bipolar cells to enable scotopic vision. Gap junctions made of connexin36 (Cx36) mediate electrical coupling among AII cells and between AII cells and ON cone bipolar cells. These gap...
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Frontiers Media S.A.
2017-12-01
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| Series: | Frontiers in Molecular Neuroscience |
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| Online Access: | http://journal.frontiersin.org/article/10.3389/fnmol.2017.00425/full |
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| author | Stephan Tetenborg Shubhash C. Yadav Sheriar G. Hormuzdi Hannah Monyer Ulrike Janssen-Bienhold Ulrike Janssen-Bienhold Karin Dedek Karin Dedek |
| author_facet | Stephan Tetenborg Shubhash C. Yadav Sheriar G. Hormuzdi Hannah Monyer Ulrike Janssen-Bienhold Ulrike Janssen-Bienhold Karin Dedek Karin Dedek |
| author_sort | Stephan Tetenborg |
| collection | DOAJ |
| description | AII amacrine cells are essential interneurons of the primary rod pathway and transmit rod-driven signals to ON cone bipolar cells to enable scotopic vision. Gap junctions made of connexin36 (Cx36) mediate electrical coupling among AII cells and between AII cells and ON cone bipolar cells. These gap junctions underlie a remarkable degree of plasticity and are modulated by different signaling cascades. In particular, Ca2+/calmodulin-dependent protein kinase II (CaMKII) has been characterized as an important regulator of Cx36, capable of potentiating electrical coupling in AII cells. However, it is unclear which CaMKII isoform mediates this effect. To obtain a more detailed understanding of the isoform composition of CaMKII at retinal gap junctions, we analyzed the retinal distribution of all four CaMKII isoforms using confocal microscopy. These experiments revealed a differential distribution of CaMKII isoforms: CaMKII-α was strongly expressed in starburst amacrine cells, which are known to lack electrical coupling. CaMKII-β was abundant in OFF bipolar cells, which form electrical synapses in the outer and the inner retina. CaMKII-γ was diffusely distributed across the entire retina and could not be assigned to a specific cell type. CaMKII-δ labeling was evident in bipolar and AII amacrine cells, which contain the majority of Cx36-immunoreactive puncta in the inner retina. We double-labeled retinas for Cx36 and the four CaMKII isoforms and revealed that the composition of the CaMKII enzyme differs between gap junctions in the outer and the inner retina: in the outer retina, only CaMKII-β colocalized with Cx36-containing gap junctions, whereas in the inner retina, CaMKII-β and -δ colocalized with Cx36. This finding suggests that gap junctions in the inner and the outer retina may be regulated differently although they both contain the same connexin. Taken together, our study identifies CaMKII-β and -δ as Cx36-specific regulators in the mouse retina with CaMKII-δ regulating the primary rod pathway. |
| first_indexed | 2024-12-16T11:02:25Z |
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| id | doaj.art-c7d0ec52b2f6462cb7484c088bca1e8c |
| institution | Directory Open Access Journal |
| issn | 1662-5099 |
| language | English |
| last_indexed | 2024-12-16T11:02:25Z |
| publishDate | 2017-12-01 |
| publisher | Frontiers Media S.A. |
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| series | Frontiers in Molecular Neuroscience |
| spelling | doaj.art-c7d0ec52b2f6462cb7484c088bca1e8c2022-12-21T22:33:58ZengFrontiers Media S.A.Frontiers in Molecular Neuroscience1662-50992017-12-011010.3389/fnmol.2017.00425318620Differential Distribution of Retinal Ca2+/Calmodulin-Dependent Kinase II (CaMKII) Isoforms Indicates CaMKII-β and -δ as Specific Elements of Electrical Synapses Made of Connexin36 (Cx36)Stephan Tetenborg0Shubhash C. Yadav1Sheriar G. Hormuzdi2Hannah Monyer3Ulrike Janssen-Bienhold4Ulrike Janssen-Bienhold5Karin Dedek6Karin Dedek7Animal Navigation/Neurosensorics, Institute for Biology and Environmental Sciences, University of Oldenburg, Oldenburg, GermanyAnimal Navigation/Neurosensorics, Institute for Biology and Environmental Sciences, University of Oldenburg, Oldenburg, GermanyDivision of Neuroscience, Ninewells Hospital and Medical School, University of Dundee, Dundee, United KingdomCancer Research Center (DKFZ), Heidelberg, GermanyVisual Neuroscience, Department of Neuroscience, University of Oldenburg, Oldenburg, GermanyResearch Center Neurosensory Science, University of Oldenburg, Oldenburg, GermanyAnimal Navigation/Neurosensorics, Institute for Biology and Environmental Sciences, University of Oldenburg, Oldenburg, GermanyResearch Center Neurosensory Science, University of Oldenburg, Oldenburg, GermanyAII amacrine cells are essential interneurons of the primary rod pathway and transmit rod-driven signals to ON cone bipolar cells to enable scotopic vision. Gap junctions made of connexin36 (Cx36) mediate electrical coupling among AII cells and between AII cells and ON cone bipolar cells. These gap junctions underlie a remarkable degree of plasticity and are modulated by different signaling cascades. In particular, Ca2+/calmodulin-dependent protein kinase II (CaMKII) has been characterized as an important regulator of Cx36, capable of potentiating electrical coupling in AII cells. However, it is unclear which CaMKII isoform mediates this effect. To obtain a more detailed understanding of the isoform composition of CaMKII at retinal gap junctions, we analyzed the retinal distribution of all four CaMKII isoforms using confocal microscopy. These experiments revealed a differential distribution of CaMKII isoforms: CaMKII-α was strongly expressed in starburst amacrine cells, which are known to lack electrical coupling. CaMKII-β was abundant in OFF bipolar cells, which form electrical synapses in the outer and the inner retina. CaMKII-γ was diffusely distributed across the entire retina and could not be assigned to a specific cell type. CaMKII-δ labeling was evident in bipolar and AII amacrine cells, which contain the majority of Cx36-immunoreactive puncta in the inner retina. We double-labeled retinas for Cx36 and the four CaMKII isoforms and revealed that the composition of the CaMKII enzyme differs between gap junctions in the outer and the inner retina: in the outer retina, only CaMKII-β colocalized with Cx36-containing gap junctions, whereas in the inner retina, CaMKII-β and -δ colocalized with Cx36. This finding suggests that gap junctions in the inner and the outer retina may be regulated differently although they both contain the same connexin. Taken together, our study identifies CaMKII-β and -δ as Cx36-specific regulators in the mouse retina with CaMKII-δ regulating the primary rod pathway.http://journal.frontiersin.org/article/10.3389/fnmol.2017.00425/fullCaMKIIgap junctionelectrical synapseconnexin36amacrine cellbipolar cell |
| spellingShingle | Stephan Tetenborg Shubhash C. Yadav Sheriar G. Hormuzdi Hannah Monyer Ulrike Janssen-Bienhold Ulrike Janssen-Bienhold Karin Dedek Karin Dedek Differential Distribution of Retinal Ca2+/Calmodulin-Dependent Kinase II (CaMKII) Isoforms Indicates CaMKII-β and -δ as Specific Elements of Electrical Synapses Made of Connexin36 (Cx36) Frontiers in Molecular Neuroscience CaMKII gap junction electrical synapse connexin36 amacrine cell bipolar cell |
| title | Differential Distribution of Retinal Ca2+/Calmodulin-Dependent Kinase II (CaMKII) Isoforms Indicates CaMKII-β and -δ as Specific Elements of Electrical Synapses Made of Connexin36 (Cx36) |
| title_full | Differential Distribution of Retinal Ca2+/Calmodulin-Dependent Kinase II (CaMKII) Isoforms Indicates CaMKII-β and -δ as Specific Elements of Electrical Synapses Made of Connexin36 (Cx36) |
| title_fullStr | Differential Distribution of Retinal Ca2+/Calmodulin-Dependent Kinase II (CaMKII) Isoforms Indicates CaMKII-β and -δ as Specific Elements of Electrical Synapses Made of Connexin36 (Cx36) |
| title_full_unstemmed | Differential Distribution of Retinal Ca2+/Calmodulin-Dependent Kinase II (CaMKII) Isoforms Indicates CaMKII-β and -δ as Specific Elements of Electrical Synapses Made of Connexin36 (Cx36) |
| title_short | Differential Distribution of Retinal Ca2+/Calmodulin-Dependent Kinase II (CaMKII) Isoforms Indicates CaMKII-β and -δ as Specific Elements of Electrical Synapses Made of Connexin36 (Cx36) |
| title_sort | differential distribution of retinal ca2 calmodulin dependent kinase ii camkii isoforms indicates camkii β and δ as specific elements of electrical synapses made of connexin36 cx36 |
| topic | CaMKII gap junction electrical synapse connexin36 amacrine cell bipolar cell |
| url | http://journal.frontiersin.org/article/10.3389/fnmol.2017.00425/full |
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