Serine/threonine kinase 17b (STK17B) signalling regulates Purkinje cell dendritic development and is altered in multiple spinocerebellar ataxias
Serine/threonine kinase 17b (STK17B, also known as DRAK2) is known to be a downstream effector of protein kinase C (PKC) in the immune system, in particular T lymphocytes. PKC activity also plays a critical role for dendritic development and synaptic maturation and plasticity in cerebellar Purkinje...
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Veröffentlicht in: | The European journal of neuroscience 2021-10, Vol.54 (7), p.6673-6684 |
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description | Serine/threonine kinase 17b (STK17B, also known as DRAK2) is known to be a downstream effector of protein kinase C (PKC) in the immune system, in particular T lymphocytes. PKC activity also plays a critical role for dendritic development and synaptic maturation and plasticity in cerebellar Purkinje cells. We present evidence that STK17B is strongly expressed in mouse cerebellar Purkinje cells starting in the early postnatal period and remaining highly expressed throughout adult stages and that STK17B is a target of PKC phosphorylation in the cerebellum. STK17B overexpression potentiates the morphological changes of Purkinje cells seen after PKC activation, suggesting that it is a downstream effector of PKC. A phosphorylation mimetic STK17B variant induced a marked reduction of Purkinje cell dendritic tree size, whereas the inhibition of STK17B with the novel compound 16 (Cpd16) could partially rescue the morphological changes of the Purkinje cell dendritic tree after PKC activation. These findings show that STK17B signalling is an important downstream effector of PKC activation in Purkinje cells. Furthermore, STK17B was identified as a molecule being transcriptionally downregulated in mouse models of SCA1, SCA7, SCA14 and SCA41. The reduced expression of STK17B in these mouse models might protect Purkinje cell dendrites from the negative effects of overactivated PKC signalling. Our findings provide new insights in the role of STK17B for Purkinje cell dendritic development and the pathology of SCAs.
In a mouse model of SCA14 with constitutive activation of PKCγ signalling, we show that serine/threonine kinase 17b (STK17B) is strongly phosphorylated and is involved in the increased downstream signalling of PKCγ. Furthermore, STK17B was identified as a molecule being dysregulated in three more mouse models of diverse types of spinocerebellar ataxias (SCAs). |
doi_str_mv | 10.1111/ejn.15465 |
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In a mouse model of SCA14 with constitutive activation of PKCγ signalling, we show that serine/threonine kinase 17b (STK17B) is strongly phosphorylated and is involved in the increased downstream signalling of PKCγ. Furthermore, STK17B was identified as a molecule being dysregulated in three more mouse models of diverse types of spinocerebellar ataxias (SCAs).</description><identifier>ISSN: 0953-816X</identifier><identifier>EISSN: 1460-9568</identifier><identifier>DOI: 10.1111/ejn.15465</identifier><identifier>PMID: 34536317</identifier><language>eng</language><publisher>France: Wiley Subscription Services, Inc</publisher><subject>Animal models ; Animals ; Apoptosis Regulatory Proteins - genetics ; Ataxin ; Cell activation ; Cell culture ; Cell size ; Cerebellar plasticity ; cerebellar Purkinje cells ; Cerebellum ; Cerebellum - metabolism ; Clinical and Translational Neuroscience ; Dendrites ; Dendritic plasticity ; DRAK2 ; Immune system ; Kinases ; Lymphocytes T ; Mice ; Morphology ; Phosphorylation ; PKCγ ; Protein kinase C ; Protein Kinase C - metabolism ; Protein Serine-Threonine Kinases - genetics ; Protein-serine/threonine kinase ; Purkinje cells ; Purkinje Cells - metabolism ; Research Report ; Serine ; Spinocerebellar ataxia ; spinocerebellar ataxias ; Spinocerebellar Ataxias - genetics ; STK17B ; Synaptic plasticity ; Synaptogenesis ; Transcription</subject><ispartof>The European journal of neuroscience, 2021-10, Vol.54 (7), p.6673-6684</ispartof><rights>2021 The Authors. published by Federation of European Neuroscience Societies and John Wiley & Sons Ltd.</rights><rights>2021 The Authors. European Journal of Neuroscience published by Federation of European Neuroscience Societies and John Wiley & Sons Ltd.</rights><rights>2021. This article is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c4435-86b5ce8310949a4fb1cb5a451a56e6ebe23bb75756d6146e7a503f20826811ec3</citedby><cites>FETCH-LOGICAL-c4435-86b5ce8310949a4fb1cb5a451a56e6ebe23bb75756d6146e7a503f20826811ec3</cites><orcidid>0000-0002-2404-5778</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1111%2Fejn.15465$$EPDF$$P50$$Gwiley$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1111%2Fejn.15465$$EHTML$$P50$$Gwiley$$Hfree_for_read</linktohtml><link.rule.ids>230,314,780,784,885,1416,27922,27923,45572,45573</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/34536317$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Wu, Qin‐Wei</creatorcontrib><creatorcontrib>Kapfhammer, Josef P.</creatorcontrib><title>Serine/threonine kinase 17b (STK17B) signalling regulates Purkinje cell dendritic development and is altered in multiple spinocerebellar ataxias</title><title>The European journal of neuroscience</title><addtitle>Eur J Neurosci</addtitle><description>Serine/threonine kinase 17b (STK17B, also known as DRAK2) is known to be a downstream effector of protein kinase C (PKC) in the immune system, in particular T lymphocytes. PKC activity also plays a critical role for dendritic development and synaptic maturation and plasticity in cerebellar Purkinje cells. We present evidence that STK17B is strongly expressed in mouse cerebellar Purkinje cells starting in the early postnatal period and remaining highly expressed throughout adult stages and that STK17B is a target of PKC phosphorylation in the cerebellum. STK17B overexpression potentiates the morphological changes of Purkinje cells seen after PKC activation, suggesting that it is a downstream effector of PKC. A phosphorylation mimetic STK17B variant induced a marked reduction of Purkinje cell dendritic tree size, whereas the inhibition of STK17B with the novel compound 16 (Cpd16) could partially rescue the morphological changes of the Purkinje cell dendritic tree after PKC activation. These findings show that STK17B signalling is an important downstream effector of PKC activation in Purkinje cells. Furthermore, STK17B was identified as a molecule being transcriptionally downregulated in mouse models of SCA1, SCA7, SCA14 and SCA41. The reduced expression of STK17B in these mouse models might protect Purkinje cell dendrites from the negative effects of overactivated PKC signalling. Our findings provide new insights in the role of STK17B for Purkinje cell dendritic development and the pathology of SCAs.
In a mouse model of SCA14 with constitutive activation of PKCγ signalling, we show that serine/threonine kinase 17b (STK17B) is strongly phosphorylated and is involved in the increased downstream signalling of PKCγ. Furthermore, STK17B was identified as a molecule being dysregulated in three more mouse models of diverse types of spinocerebellar ataxias (SCAs).</description><subject>Animal models</subject><subject>Animals</subject><subject>Apoptosis Regulatory Proteins - genetics</subject><subject>Ataxin</subject><subject>Cell activation</subject><subject>Cell culture</subject><subject>Cell size</subject><subject>Cerebellar plasticity</subject><subject>cerebellar Purkinje cells</subject><subject>Cerebellum</subject><subject>Cerebellum - metabolism</subject><subject>Clinical and Translational Neuroscience</subject><subject>Dendrites</subject><subject>Dendritic plasticity</subject><subject>DRAK2</subject><subject>Immune system</subject><subject>Kinases</subject><subject>Lymphocytes T</subject><subject>Mice</subject><subject>Morphology</subject><subject>Phosphorylation</subject><subject>PKCγ</subject><subject>Protein kinase C</subject><subject>Protein Kinase C - metabolism</subject><subject>Protein Serine-Threonine Kinases - genetics</subject><subject>Protein-serine/threonine kinase</subject><subject>Purkinje cells</subject><subject>Purkinje Cells - metabolism</subject><subject>Research Report</subject><subject>Serine</subject><subject>Spinocerebellar ataxia</subject><subject>spinocerebellar ataxias</subject><subject>Spinocerebellar Ataxias - genetics</subject><subject>STK17B</subject><subject>Synaptic plasticity</subject><subject>Synaptogenesis</subject><subject>Transcription</subject><issn>0953-816X</issn><issn>1460-9568</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2021</creationdate><recordtype>article</recordtype><sourceid>24P</sourceid><sourceid>WIN</sourceid><sourceid>EIF</sourceid><recordid>eNp1kc1u1DAUhS0EosPAghdAlti0i3Ts-CfOBgmq8lsBUovEznKcO1MPjh3spNC34JHxMKUCJLzx1fXno6NzEHpMyTEtZwXbcEwFl-IOWlAuSdUKqe6iBWkFqxSVnw_Qg5y3hBAlubiPDhgXTDLaLNCPc0guwGq6TBBDmfAXF0wGTJsOH55fvKPNiyOc3SYY713Y4ASb2ZsJMv44p8JuAVvwHvcQ-uQmZ8t0BT6OA4QJm9Bjl7HxEyQoY8DD7Cc3esB5dCHasu7Kd5Owmcx3Z_JDdG9tfIZHN_cSfXp5enHyujr78OrNyfOzynLORKVkJywoRknLW8PXHbWdMFxQIyTIolmzrmtEI2QvSyTQGEHYuiaqlopSsGyJnu11x7kboLfFbTJej8kNJl3raJz--yW4S72JV7qt23qX3xId3gik-HWGPOnB5V0UJkCcs65FwzlhUrCCPv0H3cY5lUR3lGKcKkJkoY72lE0x5wTrWzOU6F3PuvSsf_Vc2Cd_ur8lfxdbgNUe-OY8XP9fSZ--fb-X_AndrbQL</recordid><startdate>202110</startdate><enddate>202110</enddate><creator>Wu, Qin‐Wei</creator><creator>Kapfhammer, Josef P.</creator><general>Wiley Subscription Services, Inc</general><general>John Wiley and Sons Inc</general><scope>24P</scope><scope>WIN</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7QP</scope><scope>7QR</scope><scope>7TK</scope><scope>8FD</scope><scope>FR3</scope><scope>P64</scope><scope>7X8</scope><scope>5PM</scope><orcidid>https://orcid.org/0000-0002-2404-5778</orcidid></search><sort><creationdate>202110</creationdate><title>Serine/threonine kinase 17b (STK17B) signalling regulates Purkinje cell dendritic development and is altered in multiple spinocerebellar ataxias</title><author>Wu, Qin‐Wei ; Kapfhammer, Josef P.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c4435-86b5ce8310949a4fb1cb5a451a56e6ebe23bb75756d6146e7a503f20826811ec3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2021</creationdate><topic>Animal models</topic><topic>Animals</topic><topic>Apoptosis Regulatory Proteins - genetics</topic><topic>Ataxin</topic><topic>Cell activation</topic><topic>Cell culture</topic><topic>Cell size</topic><topic>Cerebellar plasticity</topic><topic>cerebellar Purkinje cells</topic><topic>Cerebellum</topic><topic>Cerebellum - metabolism</topic><topic>Clinical and Translational Neuroscience</topic><topic>Dendrites</topic><topic>Dendritic plasticity</topic><topic>DRAK2</topic><topic>Immune system</topic><topic>Kinases</topic><topic>Lymphocytes T</topic><topic>Mice</topic><topic>Morphology</topic><topic>Phosphorylation</topic><topic>PKCγ</topic><topic>Protein kinase C</topic><topic>Protein Kinase C - metabolism</topic><topic>Protein Serine-Threonine Kinases - genetics</topic><topic>Protein-serine/threonine kinase</topic><topic>Purkinje cells</topic><topic>Purkinje Cells - metabolism</topic><topic>Research Report</topic><topic>Serine</topic><topic>Spinocerebellar ataxia</topic><topic>spinocerebellar ataxias</topic><topic>Spinocerebellar Ataxias - genetics</topic><topic>STK17B</topic><topic>Synaptic plasticity</topic><topic>Synaptogenesis</topic><topic>Transcription</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Wu, Qin‐Wei</creatorcontrib><creatorcontrib>Kapfhammer, Josef P.</creatorcontrib><collection>Wiley Online Library</collection><collection>Wiley Online Library Open Access</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Calcium & Calcified Tissue Abstracts</collection><collection>Chemoreception Abstracts</collection><collection>Neurosciences Abstracts</collection><collection>Technology Research Database</collection><collection>Engineering Research Database</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>The European journal of neuroscience</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Wu, Qin‐Wei</au><au>Kapfhammer, Josef P.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Serine/threonine kinase 17b (STK17B) signalling regulates Purkinje cell dendritic development and is altered in multiple spinocerebellar ataxias</atitle><jtitle>The European journal of neuroscience</jtitle><addtitle>Eur J Neurosci</addtitle><date>2021-10</date><risdate>2021</risdate><volume>54</volume><issue>7</issue><spage>6673</spage><epage>6684</epage><pages>6673-6684</pages><issn>0953-816X</issn><eissn>1460-9568</eissn><abstract>Serine/threonine kinase 17b (STK17B, also known as DRAK2) is known to be a downstream effector of protein kinase C (PKC) in the immune system, in particular T lymphocytes. PKC activity also plays a critical role for dendritic development and synaptic maturation and plasticity in cerebellar Purkinje cells. We present evidence that STK17B is strongly expressed in mouse cerebellar Purkinje cells starting in the early postnatal period and remaining highly expressed throughout adult stages and that STK17B is a target of PKC phosphorylation in the cerebellum. STK17B overexpression potentiates the morphological changes of Purkinje cells seen after PKC activation, suggesting that it is a downstream effector of PKC. A phosphorylation mimetic STK17B variant induced a marked reduction of Purkinje cell dendritic tree size, whereas the inhibition of STK17B with the novel compound 16 (Cpd16) could partially rescue the morphological changes of the Purkinje cell dendritic tree after PKC activation. These findings show that STK17B signalling is an important downstream effector of PKC activation in Purkinje cells. Furthermore, STK17B was identified as a molecule being transcriptionally downregulated in mouse models of SCA1, SCA7, SCA14 and SCA41. The reduced expression of STK17B in these mouse models might protect Purkinje cell dendrites from the negative effects of overactivated PKC signalling. Our findings provide new insights in the role of STK17B for Purkinje cell dendritic development and the pathology of SCAs.
In a mouse model of SCA14 with constitutive activation of PKCγ signalling, we show that serine/threonine kinase 17b (STK17B) is strongly phosphorylated and is involved in the increased downstream signalling of PKCγ. Furthermore, STK17B was identified as a molecule being dysregulated in three more mouse models of diverse types of spinocerebellar ataxias (SCAs).</abstract><cop>France</cop><pub>Wiley Subscription Services, Inc</pub><pmid>34536317</pmid><doi>10.1111/ejn.15465</doi><tpages>12</tpages><orcidid>https://orcid.org/0000-0002-2404-5778</orcidid><oa>free_for_read</oa></addata></record> |
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subjects | Animal models Animals Apoptosis Regulatory Proteins - genetics Ataxin Cell activation Cell culture Cell size Cerebellar plasticity cerebellar Purkinje cells Cerebellum Cerebellum - metabolism Clinical and Translational Neuroscience Dendrites Dendritic plasticity DRAK2 Immune system Kinases Lymphocytes T Mice Morphology Phosphorylation PKCγ Protein kinase C Protein Kinase C - metabolism Protein Serine-Threonine Kinases - genetics Protein-serine/threonine kinase Purkinje cells Purkinje Cells - metabolism Research Report Serine Spinocerebellar ataxia spinocerebellar ataxias Spinocerebellar Ataxias - genetics STK17B Synaptic plasticity Synaptogenesis Transcription |
title | Serine/threonine kinase 17b (STK17B) signalling regulates Purkinje cell dendritic development and is altered in multiple spinocerebellar ataxias |
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