Regulation of KIF1A-Driven Dense Core Vesicle Transport: Ca2+/CaM Controls DCV Binding and Liprin-α/TANC2 Recruits DCVs to Postsynaptic Sites
Summary: Tight regulation of neuronal transport allows for cargo binding and release at specific cellular locations. The mechanisms by which motor proteins are loaded on vesicles and how cargoes are captured at appropriate sites remain unclear. To better understand how KIF1A-driven dense core vesicl...
| Main Authors: | , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2018-07-01
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| Series: | Cell Reports |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2211124718309987 |
| _version_ | 1818303023647031296 |
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| author | Riccardo Stucchi Gabriela Plucińska Jessica J.A. Hummel Eitan E. Zahavi Irune Guerra San Juan Oleg Klykov Richard A. Scheltema A.F. Maarten Altelaar Casper C. Hoogenraad |
| author_facet | Riccardo Stucchi Gabriela Plucińska Jessica J.A. Hummel Eitan E. Zahavi Irune Guerra San Juan Oleg Klykov Richard A. Scheltema A.F. Maarten Altelaar Casper C. Hoogenraad |
| author_sort | Riccardo Stucchi |
| collection | DOAJ |
| description | Summary: Tight regulation of neuronal transport allows for cargo binding and release at specific cellular locations. The mechanisms by which motor proteins are loaded on vesicles and how cargoes are captured at appropriate sites remain unclear. To better understand how KIF1A-driven dense core vesicle (DCV) transport is regulated, we identified the KIF1A interactome and focused on three binding partners, the calcium binding protein calmodulin (CaM) and two synaptic scaffolding proteins: liprin-α and TANC2. We showed that calcium, acting via CaM, enhances KIF1A binding to DCVs and increases vesicle motility. In contrast, liprin-α and TANC2 are not part of the KIF1A-cargo complex but capture DCVs at dendritic spines. Furthermore, we found that specific TANC2 mutations—reported in patients with different neuropsychiatric disorders—abolish the interaction with KIF1A. We propose a model in which Ca2+/CaM regulates cargo binding and liprin-α and TANC2 recruit KIF1A-transported vesicles. : Stucchi et al. show that KIF1A-dependent transport is regulated by CaM, liprin-α, and TANC2. KIF1A binding to DCVs is controlled by a Ca2+/CaM molecular mechanism, and KIF1A-driven DCVs are recruited in dendritic spines by the PSD scaffolds liprin-α and TANC2. Keywords: neuron, transport, dendritic spines, synapse, KIF1A, scaffold, calmodulin, calcium, TANC2, liprin-α |
| first_indexed | 2024-12-13T05:48:13Z |
| format | Article |
| id | doaj.art-2c5a6f74399d4c63b3fdd3228da82561 |
| institution | Directory Open Access Journal |
| issn | 2211-1247 |
| language | English |
| last_indexed | 2024-12-13T05:48:13Z |
| publishDate | 2018-07-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Cell Reports |
| spelling | doaj.art-2c5a6f74399d4c63b3fdd3228da825612022-12-21T23:57:37ZengElsevierCell Reports2211-12472018-07-01243685700Regulation of KIF1A-Driven Dense Core Vesicle Transport: Ca2+/CaM Controls DCV Binding and Liprin-α/TANC2 Recruits DCVs to Postsynaptic SitesRiccardo Stucchi0Gabriela Plucińska1Jessica J.A. Hummel2Eitan E. Zahavi3Irune Guerra San Juan4Oleg Klykov5Richard A. Scheltema6A.F. Maarten Altelaar7Casper C. Hoogenraad8Cell Biology, Department of Biology, Faculty of Science, Utrecht University, Padualaan 8, 3584 Utrecht, the Netherlands; Biomolecular Mass Spectrometry and Proteomics, Bijvoet Center for Biomolecular Research and Utrecht Institute for Pharmaceutical Sciences, Utrecht University, Padualaan 8, 3584 Utrecht, the Netherlands; Netherlands Proteomics Centre, Padualaan 8, 3584 Utrecht, the NetherlandsCell Biology, Department of Biology, Faculty of Science, Utrecht University, Padualaan 8, 3584 Utrecht, the NetherlandsCell Biology, Department of Biology, Faculty of Science, Utrecht University, Padualaan 8, 3584 Utrecht, the NetherlandsCell Biology, Department of Biology, Faculty of Science, Utrecht University, Padualaan 8, 3584 Utrecht, the NetherlandsCell Biology, Department of Biology, Faculty of Science, Utrecht University, Padualaan 8, 3584 Utrecht, the NetherlandsBiomolecular Mass Spectrometry and Proteomics, Bijvoet Center for Biomolecular Research and Utrecht Institute for Pharmaceutical Sciences, Utrecht University, Padualaan 8, 3584 Utrecht, the Netherlands; Netherlands Proteomics Centre, Padualaan 8, 3584 Utrecht, the NetherlandsBiomolecular Mass Spectrometry and Proteomics, Bijvoet Center for Biomolecular Research and Utrecht Institute for Pharmaceutical Sciences, Utrecht University, Padualaan 8, 3584 Utrecht, the Netherlands; Netherlands Proteomics Centre, Padualaan 8, 3584 Utrecht, the NetherlandsBiomolecular Mass Spectrometry and Proteomics, Bijvoet Center for Biomolecular Research and Utrecht Institute for Pharmaceutical Sciences, Utrecht University, Padualaan 8, 3584 Utrecht, the Netherlands; Netherlands Proteomics Centre, Padualaan 8, 3584 Utrecht, the NetherlandsCell Biology, Department of Biology, Faculty of Science, Utrecht University, Padualaan 8, 3584 Utrecht, the Netherlands; Corresponding authorSummary: Tight regulation of neuronal transport allows for cargo binding and release at specific cellular locations. The mechanisms by which motor proteins are loaded on vesicles and how cargoes are captured at appropriate sites remain unclear. To better understand how KIF1A-driven dense core vesicle (DCV) transport is regulated, we identified the KIF1A interactome and focused on three binding partners, the calcium binding protein calmodulin (CaM) and two synaptic scaffolding proteins: liprin-α and TANC2. We showed that calcium, acting via CaM, enhances KIF1A binding to DCVs and increases vesicle motility. In contrast, liprin-α and TANC2 are not part of the KIF1A-cargo complex but capture DCVs at dendritic spines. Furthermore, we found that specific TANC2 mutations—reported in patients with different neuropsychiatric disorders—abolish the interaction with KIF1A. We propose a model in which Ca2+/CaM regulates cargo binding and liprin-α and TANC2 recruit KIF1A-transported vesicles. : Stucchi et al. show that KIF1A-dependent transport is regulated by CaM, liprin-α, and TANC2. KIF1A binding to DCVs is controlled by a Ca2+/CaM molecular mechanism, and KIF1A-driven DCVs are recruited in dendritic spines by the PSD scaffolds liprin-α and TANC2. Keywords: neuron, transport, dendritic spines, synapse, KIF1A, scaffold, calmodulin, calcium, TANC2, liprin-αhttp://www.sciencedirect.com/science/article/pii/S2211124718309987 |
| spellingShingle | Riccardo Stucchi Gabriela Plucińska Jessica J.A. Hummel Eitan E. Zahavi Irune Guerra San Juan Oleg Klykov Richard A. Scheltema A.F. Maarten Altelaar Casper C. Hoogenraad Regulation of KIF1A-Driven Dense Core Vesicle Transport: Ca2+/CaM Controls DCV Binding and Liprin-α/TANC2 Recruits DCVs to Postsynaptic Sites Cell Reports |
| title | Regulation of KIF1A-Driven Dense Core Vesicle Transport: Ca2+/CaM Controls DCV Binding and Liprin-α/TANC2 Recruits DCVs to Postsynaptic Sites |
| title_full | Regulation of KIF1A-Driven Dense Core Vesicle Transport: Ca2+/CaM Controls DCV Binding and Liprin-α/TANC2 Recruits DCVs to Postsynaptic Sites |
| title_fullStr | Regulation of KIF1A-Driven Dense Core Vesicle Transport: Ca2+/CaM Controls DCV Binding and Liprin-α/TANC2 Recruits DCVs to Postsynaptic Sites |
| title_full_unstemmed | Regulation of KIF1A-Driven Dense Core Vesicle Transport: Ca2+/CaM Controls DCV Binding and Liprin-α/TANC2 Recruits DCVs to Postsynaptic Sites |
| title_short | Regulation of KIF1A-Driven Dense Core Vesicle Transport: Ca2+/CaM Controls DCV Binding and Liprin-α/TANC2 Recruits DCVs to Postsynaptic Sites |
| title_sort | regulation of kif1a driven dense core vesicle transport ca2 cam controls dcv binding and liprin α tanc2 recruits dcvs to postsynaptic sites |
| url | http://www.sciencedirect.com/science/article/pii/S2211124718309987 |
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