Nucleoporin Nup358 Downregulation Tunes the Neuronal Excitability in Mouse Cortical Neurons

Nucleoporins (NUPs) are proteins that comprise the nuclear pore complexes (NPCs). The NPC spans the nuclear envelope of a cell and provides a channel through which RNA and proteins move between the nucleus and the cytoplasm and vice versa. NUP and NPC disruptions have a great impact on the pathophys...

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Bibliographic Details
Published in:Life (Basel, Switzerland) Switzerland), 2023-08, Vol.13 (9), p.1791
Main Authors: Martínez-Rojas, Vladimir A, Pischedda, Francesca, Romero-Maldonado, Isabel, Khalaf, Bouchra, Piccoli, Giovanni, Macchi, Paolo, Musio, Carlo
Format: Article
Language:English
Subjects:
Ankyrins
Bioelectricity
Carbon dioxide
Channel gating
Cytoplasm
Degeneration
Down-regulation
Electric properties
Electrical properties
Excitability
Health aspects
ion channels
Kinetics
membrane excitability
Membranes
Nervous system
neurodegenerative disease
Neurodegenerative diseases
neuronal activity
Neurons
Nuclear membranes
Nuclear pores
Nucleoporins
Nucleoproteins
Pathophysiology
Proteins
Sodium channels (voltage-gated)
Software
voltage-gated sodium channels
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Summary:Nucleoporins (NUPs) are proteins that comprise the nuclear pore complexes (NPCs). The NPC spans the nuclear envelope of a cell and provides a channel through which RNA and proteins move between the nucleus and the cytoplasm and vice versa. NUP and NPC disruptions have a great impact on the pathophysiology of neurodegenerative diseases (NDDs). Although the downregulation of Nup358 leads to a reduction in the scaffold protein ankyrin-G at the axon initial segment (AIS) of mature neurons, the function of Nup358 in the cytoplasm of neurons remains elusive. To investigate whether Nup358 plays any role in neuronal activity, we downregulated Nup358 in non-pathological mouse cortical neurons and measured their active and passive bioelectrical properties. We identified that Nup358 downregulation is able to produce significant modifications of cell-membrane excitability via voltage-gated sodium channel kinetics. Our findings suggest that Nup358 contributes to neuronal excitability through a functional stabilization of the electrical properties of the neuronal membrane. Hypotheses will be discussed regarding the alteration of this active regulation as putatively occurring in the pathophysiology of NDDs.
ISSN:2075-1729
2075-1729
DOI:10.3390/life13091791