The Connection Between Rap1 and Talin1 in the Activation of Integrins in Blood Cells

Abstract

Integrins regulate the adhesion and migration of blood cells to ensure the proper positioning of these cells in the environment. Integrins detect physical and chemical stimuli in the extracellular matrix and regulate signaling pathways in blood cells that mediate their functions. Integrins are usually in a resting state in blood cells until agonist stimulation results in a high-affinity conformation (“integrin activation”), which is central to integrins’ contribution to blood cells’ trafficking and functions. In this review, we summarize the mechanisms of integrin activation in blood cells with a focus on recent advances understanding of mechanisms whereby Rap1 regulates talin1-integrin interaction to trigger integrin activation in lymphocytes, platelets, and neutrophils.

Integrin Conformational Dynamics and Mechanotransduction

“…As integrins bind the ECM, the recruitment of intracellular adaptors leads to the sequestration of more integrins, with the formation of small (10–100 nm in diameter), short lived (1–2 min) integrin clusters named nascent adhesions. Nascent adhesions either disassemble or stabilize and elongate into focal complexes (1–2 µm, lifetimes of a few minutes), with recruitment of myosin, which provides higher contractile forces [ 3 , 26 ]; recruitment of adapters, such as talin, vinculin, and α-actinin; and activation of tyrosine kinases [ 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 ]. A subset of focal complexes further mature into longer and more stable focal adhesions (several µm long, lifetimes of 10’s of minutes) that anchor large actin stress fibers to the ECM matrix [ 32 , 35 ].…”

Analysis of the Mechanism of T Lymphocytes Promoting Immune Platelet Transfusion Refractoriness by Gene Chip Technique

“…Rap1 plays a key role in TCR signal transduction and is expressed in cells by one of its two isoforms: Rap1A and Ras-related protein 1B (Rap1B) [8] . The expression of Rap1A is required for the fine-tuning of the immune response [9] . Su et al studied the effect of Rap1A deficiency on the number of T cells [10] .…”

Integrin Regulators in Neutrophils

“…Talin recruitment to the integrin cytosolic tail is mediated by the GTPase Rap1 and RIAM (gene name: amyloid-beta precursor protein-binding family b member 1 interacting protein, APBB1IP) complex [118,138]. Recent works indicate that direct Rap1-talin1 binding plays a critical role in integrin activation in platelets [118,139,140] and also regulates integrin activation in blood cells [114,140,141]. The interaction of the THD F3 with the membrane-proximal α helix of the β integrin cytoplasmic tail disrupts the connection between cytoplasmic tails [142].…”