CHIP-Dependent Regulation of the Actin Cytoskeleton is Linked to Neuronal Cell Membrane Integrity

Catarina Dias, Erisa Nita, Jakub Faktor, Ailish C. Tynan, Lenka Hernychova, Borivoj Vojtesek, Jesper Nylandsted, Ted R. Hupp, Tilo Kunath, Kathryn L. Ball

Research output: Contribution to journalArticlepeer-review

Abstract / Description of output

CHIP is an E3-ubiquitin ligase that contributes to healthy aging and has been characterised as neuroprotective. To elucidate dominant CHIP-dependent changes in protein steady-state levels in a patient derived human neuronal model, CHIP function was ablated using gene-editing and an unbiased proteomic analysis conducted to compare knock-out and wild-type isogenic iPSC-derived cortical neurons. Rather than a broad effect on protein homeostasis, loss of CHIP function impacted on a focused cohort of proteins from actin cytoskeleton signalling and membrane integrity networks. In support of the proteomics, CHIP knock-out cells had enhanced sensitivity to induced membrane damage. We conclude that the major readout of CHIP function in cortical neurons derived from iPSC of a patient with elevate -synuclein, Parkinson’s disease and dementia, is the modulation of substrates involved in maintaining cellular ‘health’. Thus, regulation of the actin cytoskeletal and membrane integrity likely contributes to the neuroprotective function(s) of CHIP.
Original languageEnglish
Pages (from-to)102878
Early online date17 Jul 2021
Publication statusE-pub ahead of print - 17 Jul 2021


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