Caveolin‐1 Phosphorylation is Essential for iPSC‐derived Human Neuronal Axonal Growth during Early Stage of Differentiation

Abstract

Proper axonal growth and guidance is essential for functional neuronal connections. Formation of aberrant neuronal connections due to genetic or epigenetic influences can contribute to neurological and mental disorders. Identification and targeting of the molecular events that promote normal neuronal growth and differentiation may promote structural and functional neuroplasticity and improve behavior in neurodegenerative diseases such as Alzheimer's disease (AD), Down syndrome, schizophrenia, and depression. Using human neurons derived from induced pluripotent stem cells (iPSCs), we show that neuron‐specific targeted (synapsin promoted, Syn) caveolin‐1 (Cav‐1) overexpression (SynCav1) significantly augmented axonal growth (SMI 31), findings akin to effects from SynCav1 murine neurons in vitro and in vivo. In contrast, neurons infected with a Cav‐1 phosphorylation mutant (SynCav1(Y14A)) exhibited stunted axonal growth. In addition, SynCav1(Y14A) significantly impaired Rac1/Cdc42CA‐mediated axonal growth. These results suggest that 1) P‐Cav‐1 is necessary for proper axonal growth during its early differentiation stage, 2) SynCav1‐mediated axonal growth is dependent upon Cav‐1 phosphorylation, 3) Rac1/Cdc42CA‐mediated neuronal growth may in part be dependent upon P‐Cav‐1. In conclusion, phosphorylation of Cav‐1 is crucial for axonal growth during early stage of differentiation in human neurons.Support or Funding InformationNS073653 (B. P. Head); Veteran Affairs Merit Award from the Department of Veterans Affairs BX003671This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.