Simiate and the focal adhesion kinase FAK1 cooperate in the regulation of dendritogenesis
Abstract Despite the crucial importance of dendritogenesis for the correct functioning of neurons, the molecular mechanisms underlying neuronal arborisation are still not well understood. Current models suggest that distinct parts and phases of dendritic development are regulated by the expression o...
| Main Authors: | , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Nature Portfolio
2022-07-01
|
| Series: | Scientific Reports |
| Online Access: | https://doi.org/10.1038/s41598-022-14460-y |
| _version_ | 1811224219478917120 |
|---|---|
| author | Ramya Rama Kristin Derlig Nina Vießmann Roman Gossmann Fabian Oriold Andreas Gießl Johann Helmut Brandstätter Ralf Enz Regina Dahlhaus |
| author_facet | Ramya Rama Kristin Derlig Nina Vießmann Roman Gossmann Fabian Oriold Andreas Gießl Johann Helmut Brandstätter Ralf Enz Regina Dahlhaus |
| author_sort | Ramya Rama |
| collection | DOAJ |
| description | Abstract Despite the crucial importance of dendritogenesis for the correct functioning of neurons, the molecular mechanisms underlying neuronal arborisation are still not well understood. Current models suggest that distinct parts and phases of dendritic development are regulated by the expression of distinct transcription factors, that are able to target the cytoskeleton. Two proteins recently implicated in dendritogenesis are the Focal Adhesion Kinase FAK1 and the Actin-binding protein Simiate. Using heterologous expression systems as well as mouse brain extracts in combination with coprecipitation assays, we show that Simiate is able to associate with FAK1. Differential centrifugation experiments further revealed the interaction to be present in cytosolic as well as nuclear fractions. Inside the nucleus though, Simiate preferentially binds to a FAK1 isoform of 80 kDa, which has previously been shown to regulate transcription factor activity. Investigating the function of both proteins in primary hippocampal cultures, we further found that FAK1 and Simiate have distinct roles in dendritogenesis: While FAK1 increases dendrite length and number, Simiate preferentially enhances growth and branching. However, if being confined to the nucleus, Simiate selectively triggers primary dendrite formation, enhancing transcription activity at the same time. Since the effect on primary dendrites is specifically re-normalized by a co-expression of FAK1 and Simiate in the nucleus, the data implies that the two proteins interact to counterbalance each other in order to control dendrite formation. Looking at the role of the cytosolic interaction of FAK1 and Simiate, we found that neurotrophin induced dendritogenesis causes a striking colocalisation of FAK1 and Simiate in dendritic growth cones, which is not present otherwise, thus suggesting that the cytosolic interaction stimulates growth cone mediated dendritogenesis in response to certain external signals. Taken together, the data show that FAK1 and Simiate exert several and distinct actions during the different phases of dendritogenesis and that these actions are related to their subcellular localisation and their interaction. |
| first_indexed | 2024-04-12T08:45:50Z |
| format | Article |
| id | doaj.art-1919afa05aba40d095d38ff312511c32 |
| institution | Directory Open Access Journal |
| issn | 2045-2322 |
| language | English |
| last_indexed | 2024-04-12T08:45:50Z |
| publishDate | 2022-07-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj.art-1919afa05aba40d095d38ff312511c322022-12-22T03:39:43ZengNature PortfolioScientific Reports2045-23222022-07-0112112510.1038/s41598-022-14460-ySimiate and the focal adhesion kinase FAK1 cooperate in the regulation of dendritogenesisRamya Rama0Kristin Derlig1Nina Vießmann2Roman Gossmann3Fabian Oriold4Andreas Gießl5Johann Helmut Brandstätter6Ralf Enz7Regina Dahlhaus8Institute for Biochemistry, Emil-Fischer Centre, Friedrich-Alexander-Universität Erlangen-NürnbergInstitute for Biochemistry, Emil-Fischer Centre, Friedrich-Alexander-Universität Erlangen-NürnbergInstitute for Biochemistry, Emil-Fischer Centre, Friedrich-Alexander-Universität Erlangen-NürnbergInstitute for Biochemistry, Emil-Fischer Centre, Friedrich-Alexander-Universität Erlangen-NürnbergInstitute for Biochemistry, Emil-Fischer Centre, Friedrich-Alexander-Universität Erlangen-NürnbergDepartment of Biology, Animal Physiology, Friedrich-Alexander-Universität Erlangen-NürnbergDepartment of Biology, Animal Physiology, Friedrich-Alexander-Universität Erlangen-NürnbergInstitute for Biochemistry, Emil-Fischer Centre, Friedrich-Alexander-Universität Erlangen-NürnbergInstitute for Biochemistry, Emil-Fischer Centre, Friedrich-Alexander-Universität Erlangen-NürnbergAbstract Despite the crucial importance of dendritogenesis for the correct functioning of neurons, the molecular mechanisms underlying neuronal arborisation are still not well understood. Current models suggest that distinct parts and phases of dendritic development are regulated by the expression of distinct transcription factors, that are able to target the cytoskeleton. Two proteins recently implicated in dendritogenesis are the Focal Adhesion Kinase FAK1 and the Actin-binding protein Simiate. Using heterologous expression systems as well as mouse brain extracts in combination with coprecipitation assays, we show that Simiate is able to associate with FAK1. Differential centrifugation experiments further revealed the interaction to be present in cytosolic as well as nuclear fractions. Inside the nucleus though, Simiate preferentially binds to a FAK1 isoform of 80 kDa, which has previously been shown to regulate transcription factor activity. Investigating the function of both proteins in primary hippocampal cultures, we further found that FAK1 and Simiate have distinct roles in dendritogenesis: While FAK1 increases dendrite length and number, Simiate preferentially enhances growth and branching. However, if being confined to the nucleus, Simiate selectively triggers primary dendrite formation, enhancing transcription activity at the same time. Since the effect on primary dendrites is specifically re-normalized by a co-expression of FAK1 and Simiate in the nucleus, the data implies that the two proteins interact to counterbalance each other in order to control dendrite formation. Looking at the role of the cytosolic interaction of FAK1 and Simiate, we found that neurotrophin induced dendritogenesis causes a striking colocalisation of FAK1 and Simiate in dendritic growth cones, which is not present otherwise, thus suggesting that the cytosolic interaction stimulates growth cone mediated dendritogenesis in response to certain external signals. Taken together, the data show that FAK1 and Simiate exert several and distinct actions during the different phases of dendritogenesis and that these actions are related to their subcellular localisation and their interaction.https://doi.org/10.1038/s41598-022-14460-y |
| spellingShingle | Ramya Rama Kristin Derlig Nina Vießmann Roman Gossmann Fabian Oriold Andreas Gießl Johann Helmut Brandstätter Ralf Enz Regina Dahlhaus Simiate and the focal adhesion kinase FAK1 cooperate in the regulation of dendritogenesis Scientific Reports |
| title | Simiate and the focal adhesion kinase FAK1 cooperate in the regulation of dendritogenesis |
| title_full | Simiate and the focal adhesion kinase FAK1 cooperate in the regulation of dendritogenesis |
| title_fullStr | Simiate and the focal adhesion kinase FAK1 cooperate in the regulation of dendritogenesis |
| title_full_unstemmed | Simiate and the focal adhesion kinase FAK1 cooperate in the regulation of dendritogenesis |
| title_short | Simiate and the focal adhesion kinase FAK1 cooperate in the regulation of dendritogenesis |
| title_sort | simiate and the focal adhesion kinase fak1 cooperate in the regulation of dendritogenesis |
| url | https://doi.org/10.1038/s41598-022-14460-y |
| work_keys_str_mv | AT ramyarama simiateandthefocaladhesionkinasefak1cooperateintheregulationofdendritogenesis AT kristinderlig simiateandthefocaladhesionkinasefak1cooperateintheregulationofdendritogenesis AT ninavießmann simiateandthefocaladhesionkinasefak1cooperateintheregulationofdendritogenesis AT romangossmann simiateandthefocaladhesionkinasefak1cooperateintheregulationofdendritogenesis AT fabianoriold simiateandthefocaladhesionkinasefak1cooperateintheregulationofdendritogenesis AT andreasgießl simiateandthefocaladhesionkinasefak1cooperateintheregulationofdendritogenesis AT johannhelmutbrandstatter simiateandthefocaladhesionkinasefak1cooperateintheregulationofdendritogenesis AT ralfenz simiateandthefocaladhesionkinasefak1cooperateintheregulationofdendritogenesis AT reginadahlhaus simiateandthefocaladhesionkinasefak1cooperateintheregulationofdendritogenesis |