Artem Efremov Lab

Discovery of force-induced Ca²⁺ signaling mediated by L-type Ca²⁺ channels in filopodia, which results in activation of Ca²⁺-sensitive calpain protease involved in the regulation of cell adhesion complexes

• Date: 2022
• Institution: Shenzhen Bay Laboratory (China), Mechanobiology Institute (Singapore)
• Authors: Artem Efremov, Ladislav Hovan, Jie Yan
• Aim of study: Filopodia are ubiquitous membrane projections that play a crucial role in guiding cell migration, utilizing yet poorly characterized mechanosensory molecular pathways. As recent studies show that Ca²⁺ channels localized to filopodia play an important role in their formation and since some Ca²⁺ channels are mechanosensitive, force-dependent behaviour of filopodial Ca2+ channels might be potentially linked to the filopodia’s mechanosensing function. To test this hypothesis, I used a combination of optical tweezers and confocal microscopy to monitoring changes in intra-filopodial Ca²⁺ levels in response to application of stretching force to individual filopodia.

Major results: It was shown that stretching forces of tens of pN strongly promote Ca²⁺ influx into filopodia, causing persistent Ca²⁺ oscillations that last for minutes even after the force is released. Several known mechanosensitive Ca²⁺ channels, such as Piezo 1, Piezo 2 and TRPV4, were found to be dispensable for the observed force-dependent Ca²⁺ influx, while L-type Ca²⁺ channels appeared to be a key player in the discovered phenomenon.

Contribution to the research field: As it has been previously demonstrated that intra-filopodial transient Ca²⁺ signals play an important role in guidance of cell migration, our results suggest that the force-induced activation of L-type Ca²⁺ channels potentially makes a major contribution to this process, providing new insights into the force-dependent function of filopodia in guidance of cell migration.