title: Differences in α-β transmembrane domain interactions among integrins enable diverging integrin signaling.
abstract: Integrins are transmembrane adhesion molecules composed of α and β 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 αIIb and β3 subunits is reversely correlated with the affinity of integrin αIIbβ3 to its ligand. Here, we examined the TMD interactions of various integrins, including α4β1, αLβ2, α5β1, αVβ1, αIIbβ3, and αVβ3. Our findings revealed that the degree of the TMD interactions in integrins α4β1 and αLβ2 expressed in immune cells was low and in integrins αIIbβ3 and αVβ3 expressed in platelets was high, while integrins α5β1 and αVβ1 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 α5β1 was restored with mutagenesis, the increase in TMD interaction inhibited the outside-in but not inside-out signaling of integrin α5β1 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.
authors.affiliation: School of Life Sciences and Biotechnology, Korea University, Seoul 136-701, Republic of Korea. chungho@korea.ac.kr
authors.forename: Chungho
authors.initials: C
authors.lastname: Kim
authors.forename: Min-Cheol
authors.initials: MC
authors.lastname: Kim
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001792:Blood Platelets / Q000378:metabolism; D016466:CHO Cells; D002448:Cell Adhesion; D002462:Cell Membrane / Q000378:metabolism; D002465:Cell Movement; D006224:Cricetinae; D005353:Fibronectins / Q000378:metabolism; D057809:HEK293 Cells; D006801:Humans; D039081:Integrin alpha5beta1 / Q000378:metabolism; D039302:Integrin alphaVbeta3 / Q000378:metabolism*; D016169:Lymphocyte Function-Associated Antigen-1 / Q000378:metabolism; D008969:Molecular Sequence Data; D010957:Plasmids / Q000378:metabolism; D019039:Platelet Glycoprotein GPIIb-IIIa Complex / Q000378:metabolism*; D011485:Protein Binding; D054730:Protein Interaction Domains and Motifs; D025941:Protein Interaction Mapping / Q000379:methods*; D016415:Sequence Alignment; D013329:Structure-Activity Relationship
chemical_list: D005353:Fibronectins; D039081:Integrin alpha5beta1; D039302:Integrin alphaVbeta3; D016169:Lymphocyte Function-Associated Antigen-1; D019039:Platelet Glycoprotein GPIIb-IIIa Complex
keywords: Integrin; Integrin activation; Migration; Outside-in signaling; Transmembrane domain