CD6 triggers actomyosin cytoskeleton remodeling after binding to its receptor complex

Area of Science:

• Immunology
• Cell Biology
• Biochemistry

Background:

• The T cell marker CD6 plays a role in inflammatory responses by interacting with receptors on target cells.
• The specific receptors for CD6 and the downstream cellular events in target cells are not fully understood.

Purpose of the Study:

• To identify novel CD6 receptors and elucidate the cellular mechanisms by which CD6 engagement affects target cells, specifically retinal pigment epithelium (RPE) cells.

Main Methods:

• Proximity labeling was used to identify potential CD6 receptors.
• Biochemical and biophysical approaches confirmed the interaction between CD6 and its receptors.
• Analysis of cytoskeletal remodeling and tight junction integrity in RPE cells upon CD6 stimulation.

Main Results:

• CD44 was identified as a novel CD6 receptor.
• CD6 binding induced the clustering of CD44, CD166, and CDCP1 on RPE cells.
• CD6 stimulation triggered actomyosin cytoskeleton remodeling via RhoA/ROCK signaling, leading to increased myosin II phosphorylation.
• This cytoskeletal activation resulted in the disassembly of tight junctions, compromising RPE barrier integrity.

Conclusions:

• CD44 is a novel receptor for CD6, forming a tripartite complex with CD166 and CDCP1.
• CD6 engagement with this complex activates RhoA/ROCK signaling, leading to actomyosin remodeling and disruption of RPE barrier function.
• These findings reveal a mechanism for T cell-mediated disruption of tissue barriers during inflammation.