The Taspase1/Myosin1f-axis regulates filopodia dynamics
Astrid Hensel1, Paul Stahl1, Lisa Moews1
1Department of Molecular Biology II, Center of Medical Biotechnology (ZMB), University Duisburg-Essen, 45141 Essen, Germany.
Abstract:
The unique threonine protease Tasp1 impacts not only ordered development and cell proliferation but also pathologies. However, its substrates and the underlying molecular mechanisms remain poorly understood. We demonstrate that the unconventional Myo1f is a Tasp1 substrate and unravel the physiological relevance of this proteolysis. We classify Myo1f as a nucleo-cytoplasmic shuttle protein, allowing its unhindered processing by nuclear Tasp1 and an association with chromatin. Moreover, we show that Myo1f induces filopodia resulting in increased cellular adhesion and migration. Importantly, filopodia formation was antagonized by Tasp1-mediated proteolysis, supported by an inverse correlation between Myo1f concentration and Tasp1 expression level. The Tasp1/Myo1f-axis might be relevant in human hematopoiesis as reduced Tasp1 expression coincided with increased Myo1f concentrations and filopodia in macrophages compared to monocytes and vice versa. In sum, we discovered Tasp1-mediated proteolysis of Myo1f as a mechanism to fine-tune filopodia formation, inter alia relevant for cells of the immune system.
Insights
The threonine protease Tasp1 cleaves the Myo1f protein, regulating cell structures called filopodia. This Tasp1-Myo1f interaction impacts cell movement and may be important in immune cell development.
Area of Science:
- Biochemistry
- Cell Biology
- Molecular Mechanisms
Background:
- The threonine protease Tasp1 plays a role in development, proliferation, and disease.
- Its substrates and molecular mechanisms are not fully understood.
Purpose of the Study:
- To identify Tasp1 substrates and elucidate the physiological relevance of their proteolysis.
- To investigate the role of the Tasp1/Myo1f interaction in cellular processes.
Main Methods:
- Proteolytic assays to identify Tasp1 substrates.
- Cellular localization studies to determine Myo1f's shuttle function.
- Analysis of filopodia formation, cell adhesion, and migration.
- Correlation studies between Tasp1 expression and Myo1f levels in immune cells.
Main Results:
- Unconventional Myo1f is identified as a Tasp1 substrate.
- Myo1f functions as a nucleo-cytoplasmic shuttle protein associated with chromatin.
- Myo1f induces filopodia, enhancing cell adhesion and migration.
- Tasp1-mediated proteolysis antagonizes Myo1f-induced filopodia formation.
- An inverse correlation exists between Myo1f concentration and Tasp1 expression.
- Reduced Tasp1 expression correlates with increased Myo1f and filopodia in macrophages versus monocytes.
Conclusions:
- Tasp1-mediated proteolysis of Myo1f is a novel mechanism for fine-tuning filopodia formation.
- This Tasp1/Myo1f pathway is potentially relevant in human hematopoiesis and immune cell function.
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