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CD13 activation assembles phosphoinositide (PI) signaling complexes to regulate the actin cytoskeleton
Emily Meredith1, Brian Aguilera1, Riya Sharma1
1Center for Vascular Biology, University of Connecticut Medical School, Farmington, CT, 06032, USA.
Scientific Reports
|January 13, 2026
Summary
Transmembrane CD13 activation drives cell protrusions that link cells and transfer signals. This pathway involves phosphoinositide regulation, impacting actin dynamics and intercellular communication.
Area of Science:
- Cell Biology
- Molecular Biology
- Biochemistry
Background:
- Transmembrane CD13 protein plays a role in cell adhesion, endocytosis, and protein recycling.
- CD13 assembles protein complexes at the plasma membrane, influencing cellular processes.
Purpose of the Study:
- To identify a novel CD13-dependent protein assembly.
- To investigate the role of this assembly in regulating phosphoinositide signaling, actin dynamics, and cell protrusions.
- To understand the mechanism of CD13-mediated intercellular communication.
Main Methods:
- Utilized CD13-expressing and CD13 knockout human Kaposi's sarcoma-derived cell lines (KSCs).
- Stimulated CD13 activation using monoclonal antibodies (mAbs).
- Analyzed cell protrusions, CD13 and actin localization, Ca2+ signal transfer, and protein complex formation via techniques like Connexin 43+ gap junction analysis.
Main Results:
- CD13 activation induced elongated cell protrusions, linking non-adjacent cells, which was diminished in CD13 knockout cells.
- Protrusion formation showed accumulation of CD13 and actin at the base.
- These protrusions facilitated Ca2+ signal transfer between connected cells via gap junctions.
- Mechanistically, CD13 activation required Src, FAK, and Cdc42 to tether IQGAP1 and ARF6, activating PI5K to increase PI(4,5)P2 levels, promoting actin polymerization.
Conclusions:
- CD13 is a novel regulator of phosphoinositide (PI) signaling.
- CD13 modulates actin cytoskeleton dynamics and membrane organization.
- CD13 facilitates intercellular communication through membrane protrusions and gap junctions.
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