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
Hauptverfasser: Wu, Qin‐Wei, Kapfhammer, Josef P.
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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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identifier ISSN: 0953-816X
ispartof The European journal of neuroscience, 2021-10, Vol.54 (7), p.6673-6684
issn 0953-816X
1460-9568
language eng
recordid cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_9292345
source Wiley-Blackwell Journals; MEDLINE
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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