TY - JOUR
T1 - Transmission of integrin β7 transmembrane domain topology enables gut lymphoid tissue development
AU - Sun, Hao
AU - Lagarrigue, Frederic
AU - Gingras, Alexandre R.
AU - Fan, Zhichao
AU - Ley, Klaus
AU - Ginsberg, Mark H.
N1 - Funding Information:
This research was supported by National Institutes of Health grants HL 078784, R35 HL 139947, and NS 092521 and by an American Heart Association postdoctoral fellowship 17POST33660181
Publisher Copyright:
© 2018 Sun et al.
PY - 2018/4/1
Y1 - 2018/4/1
N2 - Integrin activation regulates adhesion, extracellular matrix assembly, and cell migration, thereby playing an indispensable role in development and in many pathological processes. A proline mutation in the central integrin Β3 transmembrane domain (TMD) creates a flexible kink that uncouples the topology of the inner half of the TMD from the outer half. In this study, using leukocyte integrin α4β7, which enables development of gut-associated lymphoid tissue (GALT), we examined the biological effect of such a proline mutation and report that it impairs agonist-induced talin-mediated activation of integrin α4β7, thereby inhibiting rolling lymphocyte arrest, a key step in transmigration. Furthermore, the α4β7(L721P) mutation blocks lymphocyte homing to and development of the GALT. These studies show that impairing the ability of an integrin β TMD to transmit talin-induced TMD topology inhibits agonist-induced physiological integrin activation and biological function in development.
AB - Integrin activation regulates adhesion, extracellular matrix assembly, and cell migration, thereby playing an indispensable role in development and in many pathological processes. A proline mutation in the central integrin Β3 transmembrane domain (TMD) creates a flexible kink that uncouples the topology of the inner half of the TMD from the outer half. In this study, using leukocyte integrin α4β7, which enables development of gut-associated lymphoid tissue (GALT), we examined the biological effect of such a proline mutation and report that it impairs agonist-induced talin-mediated activation of integrin α4β7, thereby inhibiting rolling lymphocyte arrest, a key step in transmigration. Furthermore, the α4β7(L721P) mutation blocks lymphocyte homing to and development of the GALT. These studies show that impairing the ability of an integrin β TMD to transmit talin-induced TMD topology inhibits agonist-induced physiological integrin activation and biological function in development.
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U2 - 10.1083/jcb.201707055
DO - 10.1083/jcb.201707055
M3 - Article
C2 - 29535192
AN - SCOPUS:85044728434
SN - 0021-9525
VL - 217
SP - 1453
EP - 1465
JO - Journal of Cell Biology
JF - Journal of Cell Biology
IS - 4
ER -