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Incorporation of DDR2 clusters into collagen matrix via integrin-dependent posterior remnant tethering
Tingting Li1, Jin'e Liu1, Hao Cai2
1Jiangsu key lab of Drug Screening, Jiangsu key lab of Drug Discovery for Metabolic Disease, China Pharmaceutical University, Nanjing 210009, China.
Abstract:
Cell-matrix interactions play critical roles in cell adhesion, tissue remodeling and cancer metastasis. Discoidin domain receptor 2 (DDR2) is a collagen receptor belonging to receptor tyrosine kinase (RTK) family. It is a powerful regulator of collagen deposition in the extracellular matrix (ECM). Although the oligomerization of DDR extracellular domain (ECD) proteins can affect matrix remodeling by inhibiting fibrillogenesis, it is still unknown how cellular DDR2 is incorporated into collagen matrix. Using 3-dimentional (3D) imaging for migrating cells, we identified a novel mechanism that explains how DDR2 incorporating into collagen matrix, which we named as posterior remnant tethering. We followed the de novo formation of these remnants and identified that DDR2 clusters formed at the retracting phase of a pseudopodium, then these clusters were tethered to fibrillar collagen and peeled off from the cell body to generate DDR2 containing posterior remnants. Inhibition of β1-integrin or Rac1 activity abrogated the remnant formation. Thus, our findings unveil a special cellular mechanism for DDR2 clusters incorporating into collagen matrix in an integrin-dependent manner.
Insights
Researchers discovered a new way cells incorporate Discoidin Domain Receptor 2 (DDR2) into the collagen matrix. This "posterior remnant tethering" mechanism involves DDR2 clusters attaching to collagen as cells retract, a process dependent on integrins.
Area of Science:
- Cell biology
- Biochemistry
- Extracellular matrix research
Background:
- Cell-matrix interactions are crucial for tissue remodeling and cancer metastasis.
- Discoidin domain receptor 2 (DDR2), a receptor tyrosine kinase (RTK), regulates extracellular matrix (ECM) collagen deposition.
- The mechanism of cellular DDR2 incorporation into the collagen matrix remains unclear.
Purpose of the Study:
- To elucidate the novel mechanism by which cellular DDR2 is incorporated into the collagen matrix.
- To investigate the formation and characteristics of DDR2-containing posterior remnants during cell migration.
Main Methods:
- Utilized 3D imaging techniques to observe migrating cells and DDR2 incorporation.
- Analyzed the de novo formation of posterior remnants and DDR2 clusters.
- Investigated the role of β1-integrin and Rac1 activity in remnant formation.
Main Results:
- Identified and named a novel mechanism: posterior remnant tethering.
- Observed DDR2 clusters forming during pseudopodium retraction, tethering to fibrillar collagen, and detaching to form remnants.
- Demonstrated that inhibiting β1-integrin or Rac1 activity prevented remnant formation.
Conclusions:
- Posterior remnant tethering is a unique cellular mechanism for DDR2 incorporation into the collagen matrix.
- This process is dependent on cellular integrin activity.
- Findings provide new insights into DDR2 function in cell-matrix interactions.
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