Kidins220/<scp>ARMS</scp> transgenic lines could be instrumental in the understanding of the molecular mechanisms leading to spastic paraplegia and obesity

Cesca, Fabrizia; Schiavo, Giampietro; Benfenati, Fabio

doi:10.1111/ene.13693

Cited by 2 publications

(2 citation statements)

References 10 publications

(12 reference statements)

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“…In future studies we will address how these findings translate in vivo, under physiological and pathological conditions. In recent years, mutations in the KIDINS220 gene have been associated with severe neurodevelopmental pathologies, whose main symptoms are intellectual disability and spastic paraplegia (Cesca et al, 2018;El-Dessouky et al, 2020;Jacquemin et al, 2020;Josifova et al, 2016;Mero et al, 2017;Yang et al, 2018;Zhao et al, 2019). Within this context, the observation that Kidins220 controls astrocyte metabolism during embryonic development is instrumental to tackle the pathogenic mechanisms that underlie Kidins220-dependent neurodevelopmental diseases (i.e.…”

Section: Discussionmentioning

confidence: 99%

A developmental stage- and Kidins220-dependent switch in astrocyte responsiveness to brain-derived neurotrophic factor

Jaudon

Albini

Ferroni

et al. 2021

Journal of Cell Science

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Astroglial cells are key to maintain nervous system homeostasis. Neurotrophins are known for their pleiotropic effects on neuronal physiology, but also exert complex functions onto glial cells. In this work, we investigated: (i) the signaling competence of embryonic and postnatal primary cortical astrocytes exposed to brain-derived neurotrophic factor (BDNF); and (ii) the role of Kinase D interacting substrate (Kidins220), a transmembrane scaffold protein that mediates neurotrophin signaling in neurons, in the astrocyte response to BDNF. We found a shift from a kinase-based response in embryonic cells to a predominantly [Ca2+]i-based response in postnatal cultures associated with the decreased expression of the full-length BDNF receptor TrkB, with a contribution of Kidins220 to the BDNF-activated kinase and [Ca2+]i pathways. Finally, Kidins220 participates in astrocytes’ homeostatic function by controlling the expression of the inwardly rectifying potassium channel (Kir) 4.1 and the metabolic balance of embryonic astrocytes. Overall, our data contribute to the understanding of the complex role played by astrocytes within the central nervous system and identify Kidins220 as a novel actor in the increasing number of pathologies characterized by astrocytic dysfunctions.

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Section: Discussionmentioning

confidence: 99%

A developmental stage- and Kidins220-dependent switch in astrocyte responsiveness to brain-derived neurotrophic factor

Jaudon

Albini

Ferroni

et al. 2021

Journal of Cell Science

Self Cite

View full text Add to dashboard Cite

show abstract

“…Our future studies will address how these findings will translate in vivo, under physiological and pathological conditions. In recent years, mutations in the KIDINS220 gene have been associated with severe neurodevelopmental pathologies, whose main symptoms are intellectual disability and spastic paraplegia (55)(56)(57)(58)(59)(60)(61). A better understanding of the physiological functions of neurotrophins and Kidins220 in neurons and glial cells is instrumental to address the molecular pathways leading to this severe neurological disorder, which are currently completely unknown.…”

Section: Discussionmentioning

confidence: 99%

A developmental stage- and Kidins220/ARMS-dependent switch in astrocyte responsiveness to brain-derived neurotrophic factor

Jaudon

Albini

Ferroni

et al. 2021

Preprint

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Astroglial cells are key to maintain nervous system homeostasis, as they are able to perceive a wide variety of extracellular signals and to transduce them into responses that may be protective or disruptive toward neighboring neurons through the activation of distinct signaling pathways. Neurotrophins are a family of growth factors known for their pleiotropic effects on neuronal survival, maturation and plasticity. In this work, we investigated: (i) the signaling competence of embryonic and postnatal primary cortical astrocytes exposed to brain-derived neurotrophic factor (BDNF); and (ii) the role of the scaffold protein Kinase D interacting substrate/ankyrin repeat-rich membrane spanning (Kidins220/ARMS), a transmembrane protein that mediates neurotrophin signaling in neurons, in the astrocyte response to BDNF. We found a shift from a kinase-based response in embryonic cells to a predominantly [Ca2+]i-based response in postnatal cultures associated with the decreased expression of the full-length BDNF receptor TrkB. We also found that Kidins220/ARMS contributes to the BDNF-activated intracellular signaling in astrocytes by potentiating both kinase and [Ca2+]i pathways. Finally, Kidins220/ARMS contributes to astrocytes′ homeostatic function by controlling the expression of the inwardly rectifying potassium channel (Kir) 4.1. Overall, our data contribute to the understanding of the complex role played by astrocytes within the central nervous system and identify Kidins220/ARMS as a novel actor in the increasing number of pathologies characterized by astrocytes′ dysfunctions.

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Kidins220/ARMS transgenic lines could be instrumental in the understanding of the molecular mechanisms leading to spastic paraplegia and obesity

Cited by 2 publications

References 10 publications

A developmental stage- and Kidins220-dependent switch in astrocyte responsiveness to brain-derived neurotrophic factor

A developmental stage- and Kidins220-dependent switch in astrocyte responsiveness to brain-derived neurotrophic factor

A developmental stage- and Kidins220/ARMS-dependent switch in astrocyte responsiveness to brain-derived neurotrophic factor

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