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.
Iscience
|May 23, 2022
Summary
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.
Related Concept Videos
01:39Mechanism of Filopodia Formation
2.5K
Filopodia are thin, actin-rich cellular protrusions that play an important role in many fundamental cellular functions. They vary in their occurrence, length, and positioning in different cell types, suggesting their diverse roles.
Their main function is to guide migrating cells during normal tissue morphogenesis or cancer metastasis by recognizing and making initial contacts with the extracellular matrix. However, they can also act as stationary cell anchors or help to establish communication...
Their main function is to guide migrating cells during normal tissue morphogenesis or cancer metastasis by recognizing and making initial contacts with the extracellular matrix. However, they can also act as stationary cell anchors or help to establish communication...
2.5K
01:14Generation of Straight or Branched Actin Filaments
3.0K
The straight or branched structure formation of actin filaments is controlled by nucleating proteins such as the formins and Arp2/3 complex. Formin-mediated assembly results in straight filaments, whereas Arp2/3 protein complex-mediated assembly results in branched actin filaments.
Arp2/3 Complex
Arp2/3 complex is a seven-subunit complex consisting of two proteins similar to actin- Arp2 and Arp3, and five other subunits that help keep Arp2 and Arp3 inactive. When required, the complex is...
Arp2/3 Complex
Arp2/3 complex is a seven-subunit complex consisting of two proteins similar to actin- Arp2 and Arp3, and five other subunits that help keep Arp2 and Arp3 inactive. When required, the complex is...
3.0K
01:31Mechanism of Lamellipodia Formation
2.8K
Cells migrating in response to external stimuli form lamellipodia, which are thin membrane protrusions supported by a mesh of linked, branched, or unbranched actin filaments. These actin filaments interact with myosin motor proteins, creating the dynamic actomyosin complex within the cytoskeleton. Contractility, or the ability to generate contractile stress, is inherent to the actomyosin complex. It helps cells detect the stiffness of the surrounding ECM and exert contractile force for...
2.8K
01:19Actin Filament Depolymerization
3.2K
Actin filaments (F-actin) are composed of actin subunits. The dissociation of actin monomers can occur from either end of F-actin. The rate of dissociation is faster from the minus-end or the pointed end, where the actin subunits exist with a bound ADP, together known as ADP-actin. The depolymerization of F-actin is aided by proteins, including the actin-depolymerizing factor (ADF) and cofilin family of proteins, gelsolin, and glia maturation factor (GMF).
In F-actin, the ADF/cofilin proteins...
In F-actin, the ADF/cofilin proteins...
3.2K
01:32Cytoskeletal Coordination in Cell Migration
4.9K
A migrating cell changes its shape during the cyclic events of attachment and detachment from the substratum and repositions the cell organelles correspondingly. These complex events are orchestrated by the dynamic cytoskeletal network comprising actin filaments, intermediate filaments, and microtubules. Cytoskeletal crosstalk — the direct and indirect communication between the different components — is crucial for this coordination. Direct communication involves various linker...
4.9K
01:18Role of Myosin in Cell Migration
2.5K
Myosins are multimeric motor proteins involved in various cellular processes such as migration, adhesion, and proliferation. Myosin II is the most common type in animal cells, which binds and cross-links actin filaments.
Myosin II is a hexamer comprising two heavy chains with globular heads and coiled-coil tails, two regulatory light chains, and two essential light chains. The ATPase sites on the myosin heads hydrolyze ATP, and the released phosphate generates the force for contraction....
Myosin II is a hexamer comprising two heavy chains with globular heads and coiled-coil tails, two regulatory light chains, and two essential light chains. The ATPase sites on the myosin heads hydrolyze ATP, and the released phosphate generates the force for contraction....
2.5K