科研之友
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摘要
Integrins are transmembrane adhesion molecules composed of alpha and beta subunits. In humans, 24 integrins are expressed in a tissue-specific manner. Each integrin plays a specific role within a tissue type to control cell adhesion. We previously found that the degree of transmembrane domain (TMD) interaction between the integrin alpha IIb and beta 3 subunits is reversely correlated with the affinity of integrin alpha IIb beta 3 to its ligand. Here, we examined the TMD interactions of various integrins, including alpha 4 beta 1, alpha L beta 2, alpha 5 beta 1, alpha V beta 1, alpha IIb beta 3, and alpha V beta 3. Our findings revealed that the degree of the TMD interactions in integrins alpha 4 beta 1 and alpha L beta 2 expressed in immune cells was low and in integrins alpha IIb beta 3 and alpha V beta 3 expressed in platelets was high, while integrins alpha 5 beta 1 and alpha V beta 1 that are expressed in most adherent cells displayed intermediate TMD interactions. We identified sequence variation within the N-terminal TMD region as a factor responsible for the observed differential degree of TMD interaction among integrins. When the N-terminal interaction that was missing in integrin alpha 5 beta 1 was restored with mutagenesis, the increase in TMD interaction inhibited the outside-in but not inside-out signaling of integrin alpha 5 beta 1 and also accelerated the speed of cell migration. We suggest, therefore, that the degree of TMD interaction is designed to accommodate the specific, desired function of each integrin.
- 出版日期2013-7-5
