T-type calcium channels functionally interact with spectrin (α/β) and ankyrin B
Abstract This study describes the functional interaction between the Cav3.1 and Cav3.2 T-type calcium channels and cytoskeletal spectrin (α/β) and ankyrin B proteins. The interactions were identified utilizing a proteomic approach to identify proteins that interact with a conserved negatively charge...
| Main Authors: | , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2018-05-01
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| Series: | Molecular Brain |
| Subjects: | |
| Online Access: | http://link.springer.com/article/10.1186/s13041-018-0368-5 |
| _version_ | 1818557063768309760 |
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| author | Agustin Garcia-Caballero Fang-Xiong Zhang Victoria Hodgkinson Junting Huang Lina Chen Ivana A. Souza Stuart Cain Jennifer Kass Sascha Alles Terrance P. Snutch Gerald W. Zamponi |
| author_facet | Agustin Garcia-Caballero Fang-Xiong Zhang Victoria Hodgkinson Junting Huang Lina Chen Ivana A. Souza Stuart Cain Jennifer Kass Sascha Alles Terrance P. Snutch Gerald W. Zamponi |
| author_sort | Agustin Garcia-Caballero |
| collection | DOAJ |
| description | Abstract This study describes the functional interaction between the Cav3.1 and Cav3.2 T-type calcium channels and cytoskeletal spectrin (α/β) and ankyrin B proteins. The interactions were identified utilizing a proteomic approach to identify proteins that interact with a conserved negatively charged cytosolic region present in the carboxy-terminus of T-type calcium channels. Deletion of this stretch of amino acids decreased binding of Cav3.1 and Cav3.2 calcium channels to spectrin (α/β) and ankyrin B and notably also reduced T-type whole cell current densities in expression systems. Furthermore, fluorescence recovery after photobleaching analysis of mutant channels lacking the proximal C-terminus region revealed reduced recovery of both Cav3.1 and Cav3.2 mutant channels in hippocampal neurons. Knockdown of spectrin α and ankyrin B decreased the density of endogenous Cav3.2 in hippocampal neurons. These findings reveal spectrin (α/β) / ankyrin B cytoskeletal and signaling proteins as key regulators of T-type calcium channels expressed in the nervous system. |
| first_indexed | 2024-12-13T23:55:08Z |
| format | Article |
| id | doaj.art-ac77eff5edbc4bdca51628849a3670ac |
| institution | Directory Open Access Journal |
| issn | 1756-6606 |
| language | English |
| last_indexed | 2024-12-13T23:55:08Z |
| publishDate | 2018-05-01 |
| publisher | BMC |
| record_format | Article |
| series | Molecular Brain |
| spelling | doaj.art-ac77eff5edbc4bdca51628849a3670ac2022-12-21T23:26:36ZengBMCMolecular Brain1756-66062018-05-0111111010.1186/s13041-018-0368-5T-type calcium channels functionally interact with spectrin (α/β) and ankyrin BAgustin Garcia-Caballero0Fang-Xiong Zhang1Victoria Hodgkinson2Junting Huang3Lina Chen4Ivana A. Souza5Stuart Cain6Jennifer Kass7Sascha Alles8Terrance P. Snutch9Gerald W. Zamponi10Department of Physiology and Pharmacology, Hotchkiss Brain Institute and Alberta Children’s Hospital Research Institute, Cumming School of Medicine, University of CalgaryDepartment of Physiology and Pharmacology, Hotchkiss Brain Institute and Alberta Children’s Hospital Research Institute, Cumming School of Medicine, University of CalgaryDepartment of Physiology and Pharmacology, Hotchkiss Brain Institute and Alberta Children’s Hospital Research Institute, Cumming School of Medicine, University of CalgaryDepartment of Physiology and Pharmacology, Hotchkiss Brain Institute and Alberta Children’s Hospital Research Institute, Cumming School of Medicine, University of CalgaryDepartment of Physiology and Pharmacology, Hotchkiss Brain Institute and Alberta Children’s Hospital Research Institute, Cumming School of Medicine, University of CalgaryDepartment of Physiology and Pharmacology, Hotchkiss Brain Institute and Alberta Children’s Hospital Research Institute, Cumming School of Medicine, University of CalgaryMichael Smith Laboratories and Djavad Mowafaghian Centre for Brain Health, University of British ColombiaMichael Smith Laboratories and Djavad Mowafaghian Centre for Brain Health, University of British ColombiaMichael Smith Laboratories and Djavad Mowafaghian Centre for Brain Health, University of British ColombiaMichael Smith Laboratories and Djavad Mowafaghian Centre for Brain Health, University of British ColombiaDepartment of Physiology and Pharmacology, Hotchkiss Brain Institute and Alberta Children’s Hospital Research Institute, Cumming School of Medicine, University of CalgaryAbstract This study describes the functional interaction between the Cav3.1 and Cav3.2 T-type calcium channels and cytoskeletal spectrin (α/β) and ankyrin B proteins. The interactions were identified utilizing a proteomic approach to identify proteins that interact with a conserved negatively charged cytosolic region present in the carboxy-terminus of T-type calcium channels. Deletion of this stretch of amino acids decreased binding of Cav3.1 and Cav3.2 calcium channels to spectrin (α/β) and ankyrin B and notably also reduced T-type whole cell current densities in expression systems. Furthermore, fluorescence recovery after photobleaching analysis of mutant channels lacking the proximal C-terminus region revealed reduced recovery of both Cav3.1 and Cav3.2 mutant channels in hippocampal neurons. Knockdown of spectrin α and ankyrin B decreased the density of endogenous Cav3.2 in hippocampal neurons. These findings reveal spectrin (α/β) / ankyrin B cytoskeletal and signaling proteins as key regulators of T-type calcium channels expressed in the nervous system.http://link.springer.com/article/10.1186/s13041-018-0368-5T-type channelsSpectrin (α/β)Ankyrin BTraffickingCav3.1Cav3.2 |
| spellingShingle | Agustin Garcia-Caballero Fang-Xiong Zhang Victoria Hodgkinson Junting Huang Lina Chen Ivana A. Souza Stuart Cain Jennifer Kass Sascha Alles Terrance P. Snutch Gerald W. Zamponi T-type calcium channels functionally interact with spectrin (α/β) and ankyrin B Molecular Brain T-type channels Spectrin (α/β) Ankyrin B Trafficking Cav3.1 Cav3.2 |
| title | T-type calcium channels functionally interact with spectrin (α/β) and ankyrin B |
| title_full | T-type calcium channels functionally interact with spectrin (α/β) and ankyrin B |
| title_fullStr | T-type calcium channels functionally interact with spectrin (α/β) and ankyrin B |
| title_full_unstemmed | T-type calcium channels functionally interact with spectrin (α/β) and ankyrin B |
| title_short | T-type calcium channels functionally interact with spectrin (α/β) and ankyrin B |
| title_sort | t type calcium channels functionally interact with spectrin α β and ankyrin b |
| topic | T-type channels Spectrin (α/β) Ankyrin B Trafficking Cav3.1 Cav3.2 |
| url | http://link.springer.com/article/10.1186/s13041-018-0368-5 |
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