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The Role of LASP1 and PDLIM4 in Stress Fiber Dynamics and Mechanoresponsive Signaling

Project description

Molecular players of cell mechanosensing

The cell cytoskeleton is a dynamic network of fibres that plays a crucial role in mechanosensing, allowing cells to perceive and respond to mechanical cues in their environment. Funded by the Marie Skłodowska-Curie Actions programme, the LIM-it project aims to investigate two proteins that are associated with the actin cytoskeleton and implicated in many diseases. Their precise molecular functions are unclear, but they are known to associate with stress fibres, the contractile structures of non-muscle cells. Researchers will elucidate the mechanism by which these proteins function, enhancing our understanding of cytoskeleton organisation and mechanosensing, with potential implications for treating diseases like cancer.

Objective

The LIM domain proteins LASP1 and PDLIM4 are associated with the actin cytoskeleton, and implicated in many diseases. However, their precise molecular functions are poorly understood. Recent protein interaction studies from my host laboratory provided evidence that these two proteins associate with stress fibers (SFs), the contractile actomyosin structures of non-muscle cells. Distant homologues of LASP1 and PDLIM4 are also present in muscle sarcomeres, suggesting a potential structural role of these proteins in SFs. However, several other LIM domain proteins are involved in a wide-variety protein-protein interactions and signaling pathways, suggesting possible roles for LASP1 and PDLIM4 in signal transduction, especially in mediating mechanosensing in SFs. Indeed, previous studies proposed that LASP1 is a possible regulator of translation, whereas PDLIM4 may function as an adaptor between the cytoskeleton and kinases. The aim of my work is to elucidate the molecular functions of PDLIM4 and LASP1 using a combination of proteomics, cell biological, genetic and biochemical approaches. My specific interest is to uncover whether PDLIM4 and LASP1 are structural components of stress fibers, or if they function as mechanosensitive regulators of translation or intracellular signaling.

The findings will uncover the roles of PDLIM4 and LASP1 in cytoskeleton organization, potentially providing new insights into various diseases, including cancer. Additionally, understanding the interplay between SF-mediated mechanosensing and translation may reveal new mechanisms by which cells respond to mechanical cues. Overall, this study will broaden our understanding of SF-signaling, and has potential implications for therapeutic interventions in diseases linked to SF-dysregulation.

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HORIZON-TMA-MSCA-PF-EF - HORIZON TMA MSCA Postdoctoral Fellowships - European Fellowships

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Call for proposal

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(opens in new window) HORIZON-MSCA-2023-PF-01

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Coordinator

HELSINGIN YLIOPISTO
Net EU contribution

Net EU financial contribution. The sum of money that the participant receives, deducted by the EU contribution to its linked third party. It considers the distribution of the EU financial contribution between direct beneficiaries of the project and other types of participants, like third-party participants.

€ 199 694,40
Address
FABIANINKATU 33
00014 HELSINGIN YLIOPISTO
Finland

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Activity type
Higher or Secondary Education Establishments
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Total cost

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