The Role of LASP1 and PDLIM4 in Stress Fiber Dynamics and Mechanoresponsive Signaling
Akronym
LIM-it
Bidragets beskrivning
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.
Visa merStartår
2024
Slutår
2026
Beviljade finansiering
Beviljat belopp
199 694 €
Finansiär
Europeiska unionen
Typ av finansiering
HORIZON TMA MSCA Postdoctoral Fellowships - European Fellowships
Ramprogram
Horizon Europe (HORIZON)
Utlysning
Programdel
Marie Skłodowska-Curie Actions (MSCA) (11677Tema
MSCA Postdoctoral Fellowships 2023 (HORIZON-MSCA-2023-PF-01-01Utlysnings ID
HORIZON-MSCA-2023-PF-01 Övriga uppgifter
Finansieringsbeslutets nummer
101149024