LCP1 preferentially binds clasped αMβ2 integrin and attenuates leukocyte adhesion under flow

Area of Science:

• Cellular Biology
• Biochemistry
• Immunology

Background:

• Integrins (α/β heterodimers) exist in active and inactive states, regulated by cytoplasmic domain interactions.
• The transmembrane and cytoplasmic (TMcyto) domains of integrins are crucial for these conformational changes and protein binding.

Purpose of the Study:

• To identify integrin cytoplasmic tail-binding proteins.
• To investigate conformation-specific interactions between integrins and cytoplasmic proteins.
• To understand the role of L-plastin in integrin regulation.

Main Methods:

• Utilized lipid bicelle-incorporated integrin TMcyto domains (α5, αM, αIIb, β1, β2, β3) for protein isolation.
• Employed a clasped, lipid bicelle-incorporated αMβ2 TMcyto construct to identify conformation-specific binders.
• Investigated the binding preference of proteins to isolated versus clasped TMcyto domains.

Main Results:

• Isolated a global set of cytoplasmic proteins interacting with various integrin TMcyto domains.
• Identified L-plastin (LCP1) as a protein that preferentially binds the clasped αMβ2 TMcyto domain.
• Demonstrated that L-plastin maintains αMβ2 integrin in an inactive state *in vivo*, regulating leukocyte adhesion under flow.

Conclusions:

• Discovered conformation-specific integrin cytoplasmic interactors.
• Established L-plastin as a key regulator of αMβ2 integrin inactivation and leukocyte adhesion.
• Provided a comprehensive view of cytoplasmic protein interactions with integrin transmembrane domains.