Plexin-B2 Mediates Physiologic and Pathologic Functions of Angiogenin

Area of Science:

• Biochemistry
• Cell Biology
• Molecular Medicine

Background:

• Angiogenin (ANG) is a ribonuclease (RNase) involved in cell growth, survival, and regeneration.
• ANG requires receptor-mediated endocytosis for its functions, but its cell surface receptor was previously unidentified.

Purpose of the Study:

• To identify the functional cell surface receptor for angiogenin (ANG).
• To investigate the role of this receptor in ANG-mediated cellular processes.
• To evaluate the therapeutic potential of targeting the ANG-receptor interaction.

Main Methods:

• Functional assays using various cell types (endothelial, cancer, neuronal, hematopoietic stem and progenitor cells).
• Identification of plexin-B2 (PLXNB2) as the ANG receptor.
• In vitro and in vivo studies using antibodies against the ANG-binding site on PLXNB2.

Main Results:

• Plexin-B2 (PLXNB2) was identified as the functional receptor for ANG across multiple cell types.
• PLXNB2 mediates intracellular RNA processing, contributing to ANG's effects on cell growth, survival, and regeneration.
• Antibodies targeting the PLXNB2-ANG interaction inhibited tumor growth, promoted neuroprotection, and reduced leukemia progression.

Conclusions:

• PLXNB2 is essential for both physiological and pathological functions of ANG.
• Targeting the PLXNB2-ANG interaction offers therapeutic promise for solid and hematopoietic cancers.
• The PLXNB2-ANG pathway presents a potential therapeutic target for neurodegenerative diseases.