Abstract
Cell migration is an important process for development, homeostasis and wound healing and its deregulation leads to developmental defects and cancer metastasis. Efficient cell migration is governed by actin filament polymerisation nucleated and mediated by Arp2/3 complex. The fine-tuning of actin polymerisation requires actin regulators such as the Ena/VASP proteins (for actin elongation), and the Scar/WAVE-Arp2/3 complexes (for actin branching). There is evidence that increased Scar/WAVE-Arp2/3-mediated actin filament branching increases persistence and reduces the speed of lamellipodia. However, it is not known how lamellipodia protrusion speed and persistence translate into cell migration speed and persistence.Nance Horan Syndrome-Like 1 (NHSL1) is a member of Nance Horan Syndrome (NHS) protein family, in which mutation of the gene leads to Nance Horan syndrome, a disease characterised by dental abnormalities, developmental delay and congenital cataracts. This study focuses on two NHSL1 isoforms, called NHSL1-A and NHSL1-E. In this study, I have shown that NHSL1 interacts directly with the Scar/WAVE complex and inhibits its function on the Arp2/3 complex. NHSL1 also interacts with the Arp2/3 complex and negatively regulates its activity. Finally, NHSL1-A and NHSL1-E have opposing regulatory effects on cell migration speed, whereby NHSL1-E negatively regulates while NHSL1-A positively regulates it.
| Date of Award | 1 Mar 2024 |
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| Original language | English |
| Awarding Institution |
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| Supervisor | Matthias Krause (Supervisor) & Maria Conte (Supervisor) |