--- _id: '7875' abstract: - lang: eng text: 'Cells navigating through complex tissues face a fundamental challenge: while multiple protrusions explore different paths, the cell needs to avoid entanglement. How a cell surveys and then corrects its own shape is poorly understood. Here, we demonstrate that spatially distinct microtubule dynamics regulate amoeboid cell migration by locally promoting the retraction of protrusions. In migrating dendritic cells, local microtubule depolymerization within protrusions remote from the microtubule organizing center triggers actomyosin contractility controlled by RhoA and its exchange factor Lfc. Depletion of Lfc leads to aberrant myosin localization, thereby causing two effects that rate-limit locomotion: (1) impaired cell edge coordination during path finding and (2) defective adhesion resolution. Compromised shape control is particularly hindering in geometrically complex microenvironments, where it leads to entanglement and ultimately fragmentation of the cell body. We thus demonstrate that microtubules can act as a proprioceptive device: they sense cell shape and control actomyosin retraction to sustain cellular coherence.' acknowledged_ssus: - _id: LifeSc - _id: Bio - _id: PreCl acknowledgement: "The authors thank the Scientific Service Units (Life Sciences, Bioimaging, Preclinical) of the Institute of Science and Technology Austria for excellent support. This work was funded by the European Research Council (ERC StG 281556 and CoG 724373), two grants from the Austrian\r\nScience Fund (FWF; P29911 and DK Nanocell W1250-B20 to M. Sixt) and by the German Research Foundation (DFG SFB1032 project B09) to O. Thorn-Seshold and D. Trauner. J. Renkawitz was supported by ISTFELLOW funding from the People Program (Marie Curie Actions) of the European Union’s Seventh Framework Programme (FP7/2007-2013) under the Research Executive Agency grant agreement (291734) and a European Molecular Biology Organization long-term fellowship (ALTF 1396-2014) co-funded by the European Commission (LTFCOFUND2013, GA-2013-609409), E. Kiermaier by the Deutsche Forschungsgemeinschaft (DFG, German Research Foundation) under Germany’s Excellence Strategy—EXC 2151—390873048, and H. Hacker by the American Lebanese Syrian Associated ¨Charities. K.-D. Fischer was supported by the Analysis, Imaging and Modelling of Neuronal and Inflammatory Processes graduate school funded by the Ministry of Economics, Science, and Digitisation of the State Saxony-Anhalt and by the European Funds for Social and Regional Development." article_number: e201907154 article_processing_charge: No article_type: original author: - first_name: Aglaja full_name: Kopf, Aglaja id: 31DAC7B6-F248-11E8-B48F-1D18A9856A87 last_name: Kopf orcid: 0000-0002-2187-6656 - first_name: Jörg full_name: Renkawitz, Jörg id: 3F0587C8-F248-11E8-B48F-1D18A9856A87 last_name: Renkawitz orcid: 0000-0003-2856-3369 - first_name: Robert full_name: Hauschild, Robert id: 4E01D6B4-F248-11E8-B48F-1D18A9856A87 last_name: Hauschild orcid: 0000-0001-9843-3522 - first_name: Irute full_name: Girkontaite, Irute last_name: Girkontaite - first_name: Kerry full_name: Tedford, Kerry last_name: Tedford - first_name: Jack full_name: Merrin, Jack id: 4515C308-F248-11E8-B48F-1D18A9856A87 last_name: Merrin orcid: 0000-0001-5145-4609 - first_name: Oliver full_name: Thorn-Seshold, Oliver last_name: Thorn-Seshold - first_name: Dirk full_name: Trauner, Dirk id: E8F27F48-3EBA-11E9-92A1-B709E6697425 last_name: Trauner - first_name: Hans full_name: Häcker, Hans last_name: Häcker - first_name: Klaus Dieter full_name: Fischer, Klaus Dieter last_name: Fischer - first_name: Eva full_name: Kiermaier, Eva id: 3EB04B78-F248-11E8-B48F-1D18A9856A87 last_name: Kiermaier orcid: 0000-0001-6165-5738 - first_name: Michael K full_name: Sixt, Michael K id: 41E9FBEA-F248-11E8-B48F-1D18A9856A87 last_name: Sixt orcid: 0000-0002-6620-9179 citation: ama: Kopf A, Renkawitz J, Hauschild R, et al. Microtubules control cellular shape and coherence in amoeboid migrating cells. The Journal of Cell Biology. 2020;219(6). doi:10.1083/jcb.201907154 apa: Kopf, A., Renkawitz, J., Hauschild, R., Girkontaite, I., Tedford, K., Merrin, J., … Sixt, M. K. (2020). Microtubules control cellular shape and coherence in amoeboid migrating cells. The Journal of Cell Biology. Rockefeller University Press. https://doi.org/10.1083/jcb.201907154 chicago: Kopf, Aglaja, Jörg Renkawitz, Robert Hauschild, Irute Girkontaite, Kerry Tedford, Jack Merrin, Oliver Thorn-Seshold, et al. “Microtubules Control Cellular Shape and Coherence in Amoeboid Migrating Cells.” The Journal of Cell Biology. Rockefeller University Press, 2020. https://doi.org/10.1083/jcb.201907154. ieee: A. Kopf et al., “Microtubules control cellular shape and coherence in amoeboid migrating cells,” The Journal of Cell Biology, vol. 219, no. 6. Rockefeller University Press, 2020. ista: Kopf A, Renkawitz J, Hauschild R, Girkontaite I, Tedford K, Merrin J, Thorn-Seshold O, Trauner D, Häcker H, Fischer KD, Kiermaier E, Sixt MK. 2020. Microtubules control cellular shape and coherence in amoeboid migrating cells. The Journal of Cell Biology. 219(6), e201907154. mla: Kopf, Aglaja, et al. “Microtubules Control Cellular Shape and Coherence in Amoeboid Migrating Cells.” The Journal of Cell Biology, vol. 219, no. 6, e201907154, Rockefeller University Press, 2020, doi:10.1083/jcb.201907154. short: A. Kopf, J. Renkawitz, R. Hauschild, I. Girkontaite, K. Tedford, J. Merrin, O. Thorn-Seshold, D. Trauner, H. Häcker, K.D. Fischer, E. Kiermaier, M.K. Sixt, The Journal of Cell Biology 219 (2020). date_created: 2020-05-24T22:00:56Z date_published: 2020-06-01T00:00:00Z date_updated: 2023-08-21T06:28:17Z day: '01' ddc: - '570' department: - _id: MiSi - _id: Bio - _id: NanoFab doi: 10.1083/jcb.201907154 ec_funded: 1 external_id: isi: - '000538141100020' pmid: - '32379884' file: - access_level: open_access checksum: cb0b9c77842ae1214caade7b77e4d82d content_type: application/pdf creator: dernst date_created: 2020-11-24T13:25:13Z date_updated: 2020-11-24T13:25:13Z file_id: '8801' file_name: 2020_JCellBiol_Kopf.pdf file_size: 7536712 relation: main_file success: 1 file_date_updated: 2020-11-24T13:25:13Z has_accepted_license: '1' intvolume: ' 219' isi: 1 issue: '6' language: - iso: eng month: '06' oa: 1 oa_version: Published Version pmid: 1 project: - _id: 25A603A2-B435-11E9-9278-68D0E5697425 call_identifier: FP7 grant_number: '281556' name: Cytoskeletal force generation and force transduction of migrating leukocytes - _id: 25FE9508-B435-11E9-9278-68D0E5697425 call_identifier: H2020 grant_number: '724373' name: Cellular navigation along spatial gradients - _id: 26018E70-B435-11E9-9278-68D0E5697425 call_identifier: FWF grant_number: P29911 name: Mechanical adaptation of lamellipodial actin - _id: 252C3B08-B435-11E9-9278-68D0E5697425 call_identifier: FWF grant_number: W 1250-B20 name: Nano-Analytics of Cellular Systems - _id: 25681D80-B435-11E9-9278-68D0E5697425 call_identifier: FP7 grant_number: '291734' name: International IST Postdoc Fellowship Programme - _id: 25A48D24-B435-11E9-9278-68D0E5697425 grant_number: ALTF 1396-2014 name: Molecular and system level view of immune cell migration publication: The Journal of Cell Biology publication_identifier: eissn: - 1540-8140 publication_status: published publisher: Rockefeller University Press quality_controlled: '1' scopus_import: '1' status: public title: Microtubules control cellular shape and coherence in amoeboid migrating cells tmp: image: /images/cc_by.png legal_code_url: https://creativecommons.org/licenses/by/4.0/legalcode name: Creative Commons Attribution 4.0 International Public License (CC-BY 4.0) short: CC BY (4.0) type: journal_article user_id: 4359f0d1-fa6c-11eb-b949-802e58b17ae8 volume: 219 year: '2020' ... --- _id: '7888' abstract: - lang: eng text: Embryonic stem cell cultures are thought to self-organize into embryoid bodies, able to undergo symmetry-breaking, germ layer specification and even morphogenesis. Yet, it is unclear how to reconcile this remarkable self-organization capacity with classical experiments demonstrating key roles for extrinsic biases by maternal factors and/or extraembryonic tissues in embryogenesis. Here, we show that zebrafish embryonic tissue explants, prepared prior to germ layer induction and lacking extraembryonic tissues, can specify all germ layers and form a seemingly complete mesendoderm anlage. Importantly, explant organization requires polarized inheritance of maternal factors from dorsal-marginal regions of the blastoderm. Moreover, induction of endoderm and head-mesoderm, which require peak Nodal-signaling levels, is highly variable in explants, reminiscent of embryos with reduced Nodal signals from the extraembryonic tissues. Together, these data suggest that zebrafish explants do not undergo bona fide self-organization, but rather display features of genetically encoded self-assembly, where intrinsic genetic programs control the emergence of order. article_number: e55190 article_processing_charge: No article_type: original author: - first_name: Alexandra full_name: Schauer, Alexandra id: 30A536BA-F248-11E8-B48F-1D18A9856A87 last_name: Schauer orcid: 0000-0001-7659-9142 - first_name: Diana C full_name: Nunes Pinheiro, Diana C id: 2E839F16-F248-11E8-B48F-1D18A9856A87 last_name: Nunes Pinheiro orcid: 0000-0003-4333-7503 - first_name: Robert full_name: Hauschild, Robert id: 4E01D6B4-F248-11E8-B48F-1D18A9856A87 last_name: Hauschild orcid: 0000-0001-9843-3522 - first_name: Carl-Philipp J full_name: Heisenberg, Carl-Philipp J id: 39427864-F248-11E8-B48F-1D18A9856A87 last_name: Heisenberg orcid: 0000-0002-0912-4566 citation: ama: Schauer A, Nunes Pinheiro DC, Hauschild R, Heisenberg C-PJ. Zebrafish embryonic explants undergo genetically encoded self-assembly. eLife. 2020;9. doi:10.7554/elife.55190 apa: Schauer, A., Nunes Pinheiro, D. C., Hauschild, R., & Heisenberg, C.-P. J. (2020). Zebrafish embryonic explants undergo genetically encoded self-assembly. ELife. eLife Sciences Publications. https://doi.org/10.7554/elife.55190 chicago: Schauer, Alexandra, Diana C Nunes Pinheiro, Robert Hauschild, and Carl-Philipp J Heisenberg. “Zebrafish Embryonic Explants Undergo Genetically Encoded Self-Assembly.” ELife. eLife Sciences Publications, 2020. https://doi.org/10.7554/elife.55190. ieee: A. Schauer, D. C. Nunes Pinheiro, R. Hauschild, and C.-P. J. Heisenberg, “Zebrafish embryonic explants undergo genetically encoded self-assembly,” eLife, vol. 9. eLife Sciences Publications, 2020. ista: Schauer A, Nunes Pinheiro DC, Hauschild R, Heisenberg C-PJ. 2020. Zebrafish embryonic explants undergo genetically encoded self-assembly. eLife. 9, e55190. mla: Schauer, Alexandra, et al. “Zebrafish Embryonic Explants Undergo Genetically Encoded Self-Assembly.” ELife, vol. 9, e55190, eLife Sciences Publications, 2020, doi:10.7554/elife.55190. short: A. Schauer, D.C. Nunes Pinheiro, R. Hauschild, C.-P.J. Heisenberg, ELife 9 (2020). date_created: 2020-05-25T15:01:40Z date_published: 2020-04-06T00:00:00Z date_updated: 2023-08-21T06:25:49Z day: '06' ddc: - '570' department: - _id: CaHe - _id: Bio doi: 10.7554/elife.55190 ec_funded: 1 external_id: isi: - '000531544400001' pmid: - '32250246' file: - access_level: open_access checksum: f6aad884cf706846ae9357fcd728f8b5 content_type: application/pdf creator: dernst date_created: 2020-05-25T15:15:43Z date_updated: 2020-07-14T12:48:04Z file_id: '7890' file_name: 2020_eLife_Schauer.pdf file_size: 7744848 relation: main_file file_date_updated: 2020-07-14T12:48:04Z has_accepted_license: '1' intvolume: ' 9' isi: 1 language: - iso: eng month: '04' oa: 1 oa_version: Published Version pmid: 1 project: - _id: 260F1432-B435-11E9-9278-68D0E5697425 call_identifier: H2020 grant_number: '742573' name: Interaction and feedback between cell mechanics and fate specification in vertebrate gastrulation - _id: 26B1E39C-B435-11E9-9278-68D0E5697425 grant_number: '25239' name: 'Mesendoderm specification in zebrafish: The role of extraembryonic tissues' - _id: 26520D1E-B435-11E9-9278-68D0E5697425 grant_number: ALTF 850-2017 name: Coordination of mesendoderm cell fate specification and internalization during zebrafish gastrulation - _id: 266BC5CE-B435-11E9-9278-68D0E5697425 grant_number: LT000429 name: Coordination of mesendoderm fate specification and internalization during zebrafish gastrulation publication: eLife publication_identifier: issn: - 2050-084X publication_status: published publisher: eLife Sciences Publications quality_controlled: '1' related_material: record: - id: '12891' relation: dissertation_contains status: public scopus_import: '1' status: public title: Zebrafish embryonic explants undergo genetically encoded self-assembly tmp: image: /images/cc_by.png legal_code_url: https://creativecommons.org/licenses/by/4.0/legalcode name: Creative Commons Attribution 4.0 International Public License (CC-BY 4.0) short: CC BY (4.0) type: journal_article user_id: 4359f0d1-fa6c-11eb-b949-802e58b17ae8 volume: 9 year: '2020' ... --- _id: '7877' abstract: - lang: eng text: The NIPBL/MAU2 heterodimer loads cohesin onto chromatin. Mutations inNIPBLaccount for most cases ofthe rare developmental disorder Cornelia de Lange syndrome (CdLS). Here we report aMAU2 variant causing CdLS, a deletion of seven amino acids that impairs the interaction between MAU2 and the NIPBL N terminus.Investigating this interaction, we discovered that MAU2 and the NIPBL N terminus are largely dispensable fornormal cohesin and NIPBL function in cells with a NIPBL early truncating mutation. Despite a predicted fataloutcome of an out-of-frame single nucleotide duplication inNIPBL, engineered in two different cell lines,alternative translation initiation yields a form of NIPBL missing N-terminal residues. This form cannot interactwith MAU2, but binds DNA and mediates cohesin loading. Altogether, our work reveals that cohesin loading can occur independently of functional NIPBL/MAU2 complexes and highlights a novel mechanism protectiveagainst out-of-frame mutations that is potentially relevant for other genetic conditions. article_number: '107647' article_processing_charge: No article_type: original author: - first_name: Ilaria full_name: Parenti, Ilaria id: D93538B0-5B71-11E9-AC62-02EBE5697425 last_name: Parenti - first_name: Farah full_name: Diab, Farah last_name: Diab - first_name: Sara Ruiz full_name: Gil, Sara Ruiz last_name: Gil - first_name: Eskeatnaf full_name: Mulugeta, Eskeatnaf last_name: Mulugeta - first_name: Valentina full_name: Casa, Valentina last_name: Casa - first_name: Riccardo full_name: Berutti, Riccardo last_name: Berutti - first_name: Rutger W.W. full_name: Brouwer, Rutger W.W. last_name: Brouwer - first_name: Valerie full_name: Dupé, Valerie last_name: Dupé - first_name: Juliane full_name: Eckhold, Juliane last_name: Eckhold - first_name: Elisabeth full_name: Graf, Elisabeth last_name: Graf - first_name: Beatriz full_name: Puisac, Beatriz last_name: Puisac - first_name: Feliciano full_name: Ramos, Feliciano last_name: Ramos - first_name: Thomas full_name: Schwarzmayr, Thomas last_name: Schwarzmayr - first_name: Macarena Moronta full_name: Gines, Macarena Moronta last_name: Gines - first_name: Thomas full_name: Van Staveren, Thomas last_name: Van Staveren - first_name: Wilfred F.J. full_name: Van Ijcken, Wilfred F.J. last_name: Van Ijcken - first_name: Tim M. full_name: Strom, Tim M. last_name: Strom - first_name: Juan full_name: Pié, Juan last_name: Pié - first_name: Erwan full_name: Watrin, Erwan last_name: Watrin - first_name: Frank J. full_name: Kaiser, Frank J. last_name: Kaiser - first_name: Kerstin S. full_name: Wendt, Kerstin S. last_name: Wendt citation: ama: Parenti I, Diab F, Gil SR, et al. MAU2 and NIPBL variants impair the heterodimerization of the cohesin loader subunits and cause Cornelia de Lange syndrome. Cell Reports. 2020;31(7). doi:10.1016/j.celrep.2020.107647 apa: Parenti, I., Diab, F., Gil, S. R., Mulugeta, E., Casa, V., Berutti, R., … Wendt, K. S. (2020). MAU2 and NIPBL variants impair the heterodimerization of the cohesin loader subunits and cause Cornelia de Lange syndrome. Cell Reports. Elsevier. https://doi.org/10.1016/j.celrep.2020.107647 chicago: Parenti, Ilaria, Farah Diab, Sara Ruiz Gil, Eskeatnaf Mulugeta, Valentina Casa, Riccardo Berutti, Rutger W.W. Brouwer, et al. “MAU2 and NIPBL Variants Impair the Heterodimerization of the Cohesin Loader Subunits and Cause Cornelia de Lange Syndrome.” Cell Reports. Elsevier, 2020. https://doi.org/10.1016/j.celrep.2020.107647. ieee: I. Parenti et al., “MAU2 and NIPBL variants impair the heterodimerization of the cohesin loader subunits and cause Cornelia de Lange syndrome,” Cell Reports, vol. 31, no. 7. Elsevier, 2020. ista: Parenti I, Diab F, Gil SR, Mulugeta E, Casa V, Berutti R, Brouwer RWW, Dupé V, Eckhold J, Graf E, Puisac B, Ramos F, Schwarzmayr T, Gines MM, Van Staveren T, Van Ijcken WFJ, Strom TM, Pié J, Watrin E, Kaiser FJ, Wendt KS. 2020. MAU2 and NIPBL variants impair the heterodimerization of the cohesin loader subunits and cause Cornelia de Lange syndrome. Cell Reports. 31(7), 107647. mla: Parenti, Ilaria, et al. “MAU2 and NIPBL Variants Impair the Heterodimerization of the Cohesin Loader Subunits and Cause Cornelia de Lange Syndrome.” Cell Reports, vol. 31, no. 7, 107647, Elsevier, 2020, doi:10.1016/j.celrep.2020.107647. short: I. Parenti, F. Diab, S.R. Gil, E. Mulugeta, V. Casa, R. Berutti, R.W.W. Brouwer, V. Dupé, J. Eckhold, E. Graf, B. Puisac, F. Ramos, T. Schwarzmayr, M.M. Gines, T. Van Staveren, W.F.J. Van Ijcken, T.M. Strom, J. Pié, E. Watrin, F.J. Kaiser, K.S. Wendt, Cell Reports 31 (2020). date_created: 2020-05-24T22:00:57Z date_published: 2020-05-19T00:00:00Z date_updated: 2023-08-21T06:27:47Z day: '19' ddc: - '570' department: - _id: GaNo doi: 10.1016/j.celrep.2020.107647 external_id: isi: - '000535655200005' file: - access_level: open_access checksum: 64d8f7467731ee5c166b10b939b8310b content_type: application/pdf creator: dernst date_created: 2020-05-26T11:05:01Z date_updated: 2020-07-14T12:48:04Z file_id: '7892' file_name: 2020_CellReports_Parenti.pdf file_size: 4695682 relation: main_file file_date_updated: 2020-07-14T12:48:04Z has_accepted_license: '1' intvolume: ' 31' isi: 1 issue: '7' language: - iso: eng month: '05' oa: 1 oa_version: Published Version publication: Cell Reports publication_identifier: eissn: - '22111247' publication_status: published publisher: Elsevier quality_controlled: '1' scopus_import: '1' status: public title: MAU2 and NIPBL variants impair the heterodimerization of the cohesin loader subunits and cause Cornelia de Lange syndrome tmp: image: /images/cc_by_nc_nd.png legal_code_url: https://creativecommons.org/licenses/by-nc-nd/4.0/legalcode name: Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0) short: CC BY-NC-ND (4.0) type: journal_article user_id: 4359f0d1-fa6c-11eb-b949-802e58b17ae8 volume: 31 year: '2020' ... --- _id: '7878' abstract: - lang: eng text: Type 1 metabotropic glutamate receptors (mGluR1s) are key elements in neuronal signaling. While their function is well documented in slices, requirements for their activation in vivo are poorly understood. We examine this question in adult mice in vivo using 2-photon imaging of cerebellar molecular layer interneurons (MLIs) expressing GCaMP. In anesthetized mice, parallel fiber activation evokes beam-like Cai rises in postsynaptic MLIs which depend on co-activation of mGluR1s and ionotropic glutamate receptors (iGluRs). In awake mice, blocking mGluR1 decreases Cai rises associated with locomotion. In vitro studies and freeze-fracture electron microscopy show that the iGluR-mGluR1 interaction is synergistic and favored by close association of the two classes of receptors. Altogether our results suggest that mGluR1s, acting in synergy with iGluRs, potently contribute to processing cerebellar neuronal signaling under physiological conditions. article_number: e56839 article_processing_charge: No article_type: original author: - first_name: Jin full_name: Bao, Jin last_name: Bao - first_name: Michael full_name: Graupner, Michael last_name: Graupner - first_name: Guadalupe full_name: Astorga, Guadalupe last_name: Astorga - first_name: Thibault full_name: Collin, Thibault last_name: Collin - first_name: Abdelali full_name: Jalil, Abdelali last_name: Jalil - first_name: Dwi Wahyu full_name: Indriati, Dwi Wahyu last_name: Indriati - first_name: Jonathan full_name: Bradley, Jonathan last_name: Bradley - first_name: Ryuichi full_name: Shigemoto, Ryuichi id: 499F3ABC-F248-11E8-B48F-1D18A9856A87 last_name: Shigemoto orcid: 0000-0001-8761-9444 - first_name: Isabel full_name: Llano, Isabel last_name: Llano citation: ama: Bao J, Graupner M, Astorga G, et al. Synergism of type 1 metabotropic and ionotropic glutamate receptors in cerebellar molecular layer interneurons in vivo. eLife. 2020;9. doi:10.7554/eLife.56839 apa: Bao, J., Graupner, M., Astorga, G., Collin, T., Jalil, A., Indriati, D. W., … Llano, I. (2020). Synergism of type 1 metabotropic and ionotropic glutamate receptors in cerebellar molecular layer interneurons in vivo. ELife. eLife Sciences Publications. https://doi.org/10.7554/eLife.56839 chicago: Bao, Jin, Michael Graupner, Guadalupe Astorga, Thibault Collin, Abdelali Jalil, Dwi Wahyu Indriati, Jonathan Bradley, Ryuichi Shigemoto, and Isabel Llano. “Synergism of Type 1 Metabotropic and Ionotropic Glutamate Receptors in Cerebellar Molecular Layer Interneurons in Vivo.” ELife. eLife Sciences Publications, 2020. https://doi.org/10.7554/eLife.56839. ieee: J. Bao et al., “Synergism of type 1 metabotropic and ionotropic glutamate receptors in cerebellar molecular layer interneurons in vivo,” eLife, vol. 9. eLife Sciences Publications, 2020. ista: Bao J, Graupner M, Astorga G, Collin T, Jalil A, Indriati DW, Bradley J, Shigemoto R, Llano I. 2020. Synergism of type 1 metabotropic and ionotropic glutamate receptors in cerebellar molecular layer interneurons in vivo. eLife. 9, e56839. mla: Bao, Jin, et al. “Synergism of Type 1 Metabotropic and Ionotropic Glutamate Receptors in Cerebellar Molecular Layer Interneurons in Vivo.” ELife, vol. 9, e56839, eLife Sciences Publications, 2020, doi:10.7554/eLife.56839. short: J. Bao, M. Graupner, G. Astorga, T. Collin, A. Jalil, D.W. Indriati, J. Bradley, R. Shigemoto, I. Llano, ELife 9 (2020). date_created: 2020-05-24T22:00:58Z date_published: 2020-05-13T00:00:00Z date_updated: 2023-08-21T06:26:50Z day: '13' ddc: - '570' department: - _id: RySh doi: 10.7554/eLife.56839 external_id: isi: - '000535191600001' pmid: - '32401196' file: - access_level: open_access checksum: 8ea99bb6660cc407dbdb00c173b01683 content_type: application/pdf creator: dernst date_created: 2020-05-26T09:34:54Z date_updated: 2020-07-14T12:48:04Z file_id: '7891' file_name: 2020_eLife_Bao.pdf file_size: 4832050 relation: main_file file_date_updated: 2020-07-14T12:48:04Z has_accepted_license: '1' intvolume: ' 9' isi: 1 language: - iso: eng month: '05' oa: 1 oa_version: Published Version pmid: 1 publication: eLife publication_identifier: eissn: - 2050084X publication_status: published publisher: eLife Sciences Publications quality_controlled: '1' scopus_import: '1' status: public title: Synergism of type 1 metabotropic and ionotropic glutamate receptors in cerebellar molecular layer interneurons in vivo tmp: image: /images/cc_by.png legal_code_url: https://creativecommons.org/licenses/by/4.0/legalcode name: Creative Commons Attribution 4.0 International Public License (CC-BY 4.0) short: CC BY (4.0) type: journal_article user_id: 4359f0d1-fa6c-11eb-b949-802e58b17ae8 volume: 9 year: '2020' ... --- _id: '7880' abstract: - lang: eng text: 'Following its evoked release, dopamine (DA) signaling is rapidly terminated by presynaptic reuptake, mediated by the cocaine-sensitive DA transporter (DAT). DAT surface availability is dynamically regulated by endocytic trafficking, and direct protein kinase C (PKC) activation acutely diminishes DAT surface expression by accelerating DAT internalization. Previous cell line studies demonstrated that PKC-stimulated DAT endocytosis requires both Ack1 inactivation, which releases a DAT-specific endocytic brake, and the neuronal GTPase, Rit2, which binds DAT. However, it is unknown whether Rit2 is required for PKC-stimulated DAT endocytosis in DAergic terminals or whether there are region- and/or sex-dependent differences in PKC-stimulated DAT trafficking. Moreover, the mechanisms by which Rit2 controls PKC-stimulated DAT endocytosis are unknown. Here, we directly examined these important questions. Ex vivo studies revealed that PKC activation acutely decreased DAT surface expression selectively in ventral, but not dorsal, striatum. AAV-mediated, conditional Rit2 knockdown in DAergic neurons impacted baseline DAT surface:intracellular distribution in DAergic terminals from female ventral, but not dorsal, striatum. Further, Rit2 was required for PKC-stimulated DAT internalization in both male and female ventral striatum. FRET and surface pulldown studies in cell lines revealed that PKC activation drives DAT-Rit2 surface dissociation and that the DAT N terminus is required for both PKC-mediated DAT-Rit2 dissociation and DAT internalization. Finally, we found that Rit2 and Ack1 independently converge on DAT to facilitate PKC-stimulated DAT endocytosis. Together, our data provide greater insight into mechanisms that mediate PKC-regulated DAT internalization and reveal unexpected region-specific differences in PKC-stimulated DAT trafficking in bona fide DAergic terminals. ' article_processing_charge: No article_type: original author: - first_name: Rita R. full_name: Fagan, Rita R. last_name: Fagan - first_name: Patrick J. full_name: Kearney, Patrick J. last_name: Kearney - first_name: Carolyn G. full_name: Sweeney, Carolyn G. last_name: Sweeney - first_name: Dino full_name: Luethi, Dino last_name: Luethi - first_name: Florianne E full_name: Schoot Uiterkamp, Florianne E id: 3526230C-F248-11E8-B48F-1D18A9856A87 last_name: Schoot Uiterkamp - first_name: Klaus full_name: Schicker, Klaus last_name: Schicker - first_name: Brian S. full_name: Alejandro, Brian S. last_name: Alejandro - first_name: Lauren C. full_name: O'Connor, Lauren C. last_name: O'Connor - first_name: Harald H. full_name: Sitte, Harald H. last_name: Sitte - first_name: Haley E. full_name: Melikian, Haley E. last_name: Melikian citation: ama: 'Fagan RR, Kearney PJ, Sweeney CG, et al. Dopamine transporter trafficking and Rit2 GTPase: Mechanism of action and in vivo impact. Journal of Biological Chemistry. 2020;295(16):5229-5244. doi:10.1074/jbc.RA120.012628' apa: 'Fagan, R. R., Kearney, P. J., Sweeney, C. G., Luethi, D., Schoot Uiterkamp, F. E., Schicker, K., … Melikian, H. E. (2020). Dopamine transporter trafficking and Rit2 GTPase: Mechanism of action and in vivo impact. Journal of Biological Chemistry. ASBMB Publications. https://doi.org/10.1074/jbc.RA120.012628' chicago: 'Fagan, Rita R., Patrick J. Kearney, Carolyn G. Sweeney, Dino Luethi, Florianne E Schoot Uiterkamp, Klaus Schicker, Brian S. Alejandro, Lauren C. O’Connor, Harald H. Sitte, and Haley E. Melikian. “Dopamine Transporter Trafficking and Rit2 GTPase: Mechanism of Action and in Vivo Impact.” Journal of Biological Chemistry. ASBMB Publications, 2020. https://doi.org/10.1074/jbc.RA120.012628.' ieee: 'R. R. Fagan et al., “Dopamine transporter trafficking and Rit2 GTPase: Mechanism of action and in vivo impact,” Journal of Biological Chemistry, vol. 295, no. 16. ASBMB Publications, pp. 5229–5244, 2020.' ista: 'Fagan RR, Kearney PJ, Sweeney CG, Luethi D, Schoot Uiterkamp FE, Schicker K, Alejandro BS, O’Connor LC, Sitte HH, Melikian HE. 2020. Dopamine transporter trafficking and Rit2 GTPase: Mechanism of action and in vivo impact. Journal of Biological Chemistry. 295(16), 5229–5244.' mla: 'Fagan, Rita R., et al. “Dopamine Transporter Trafficking and Rit2 GTPase: Mechanism of Action and in Vivo Impact.” Journal of Biological Chemistry, vol. 295, no. 16, ASBMB Publications, 2020, pp. 5229–44, doi:10.1074/jbc.RA120.012628.' short: R.R. Fagan, P.J. Kearney, C.G. Sweeney, D. Luethi, F.E. Schoot Uiterkamp, K. Schicker, B.S. Alejandro, L.C. O’Connor, H.H. Sitte, H.E. Melikian, Journal of Biological Chemistry 295 (2020) 5229–5244. date_created: 2020-05-24T22:00:59Z date_published: 2020-04-17T00:00:00Z date_updated: 2023-08-21T06:26:22Z day: '17' department: - _id: SaSi doi: 10.1074/jbc.RA120.012628 external_id: isi: - '000530288000006' pmid: - '32132171' intvolume: ' 295' isi: 1 issue: '16' language: - iso: eng main_file_link: - open_access: '1' url: https://escholarship.umassmed.edu/oapubs/4187 month: '04' oa: 1 oa_version: Submitted Version page: 5229-5244 pmid: 1 publication: Journal of Biological Chemistry publication_identifier: eissn: - 1083351X issn: - '00219258' publication_status: published publisher: ASBMB Publications quality_controlled: '1' scopus_import: '1' status: public title: 'Dopamine transporter trafficking and Rit2 GTPase: Mechanism of action and in vivo impact' type: journal_article user_id: 4359f0d1-fa6c-11eb-b949-802e58b17ae8 volume: 295 year: '2020' ...