Caveolin-1 Phosphorylation Is Essential for Axonal Growth of Human Neurons Derived From iPSCs

Frontiers in Cellular Neuroscience
Shanshan WangBrian P Head

Abstract

Proper axonal growth and guidance is essential for neuron differentiation and development. Abnormal neuronal development due to genetic or epigenetic influences can contribute to neurological and mental disorders such as Down syndrome, Rett syndrome, and autism. Identification of the molecular targets that promote proper neuronal growth and differentiation may restore structural and functional neuroplasticity, thus improving functional performance in neurodevelopmental disorders. Using differentiated human neuronal progenitor cells (NPCs) derived from induced pluripotent stem cells (iPSCs), the present study demonstrates that during early stage differentiation of human NPCs, neuron-targeted overexpression constitutively active Rac1 (Rac1CA) and constitutively active Cdc42 (Cdc42CA) enhance expression of P-Cav-1, T-Cav-1, and P-cofilin and increases axonal growth. Similarly, neuron-targeted over-expression of Cav-1 (termed SynCav1) increases axonal development by increasing both axon length and volume. Moreover, inhibition of Cav-1(Y14A) phosphorylation blunts Rac1/Cdc42-mediated both axonal growth and differentiation of human NPCs and SynCav1(Y14A)-treated NPCs exhibited blunted axonal growth. These results suggest that: (1) Sy...Continue Reading

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Nov 17, 2020·Frontiers in Cell and Developmental Biology·Maria DudãuMihail E Hinescu
Apr 2, 2021·Journal of Proteome Research·Andres Di PaoloJosé Sotelo Silveira
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Sep 10, 2021·Journal of Cancer Research and Clinical Oncology·Xingning LaiLixia Xiong

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Datasets Mentioned

BETA
GM25430

Methods Mentioned

BETA
GTPases
GTPase
protein assay
transfection

Software Mentioned

Neurolucida
Prism
Image J
Autoneuron
GraphPad

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