Open AccessThe Role of the Cytoplasmic Domain of α6 Integrin in the Assembly and Function of α6β1 and α6β4
Author(s) -
Melker Anneinieke A.,
Sonnenberg Arnoud
Publication year - 1996
Publication title -
european journal of biochemistry
Language(s) - English
Resource type - Journals
eISSN - 1432-1033
pISSN - 0014-2956
DOI - 10.1111/j.1432-1033.1996.0254t.x
Subject(s) - cytoplasm , beta (programming language) , integrin , alpha (finance) , g alpha subunit , microbiology and biotechnology , interleukin 5 receptor alpha subunit , complementary dna , transfection , endoplasmic reticulum , biology , chemistry , protein subunit , receptor , cell culture , biochemistry , gene , genetics , medicine , construct validity , nursing , computer science , patient satisfaction , programming language
We have studied the role of the cytoplasmic domain of α6 in the assembly and function of the α6β4 integrin, and compared it with the role of α6 in the assembly and function of α6β1, by transfection of cDNAs encoding cytoplasmic mutants of α6 into K562 cells with or without full‐length β4 cDNA. Des‐(1022–1050)‐α6, which contains a deletion C‐terminal to the GFFKR motif, was expressed in association with β1, but associated preferentially with β4, whereas the wild‐type α6 subunit associated efficiently with β1 and β4 Des‐(1016–1050)‐α6, which lacked also the GFFKR sequence, was only expressed at the cell surface when β4 was available. Transient expression in COS‐7 cells showed that des‐(1016–1050)‐α6 was retained in the endoplasmic reticulum as a monomer, which suggests that truncation of the cytoplasmic domain reduces the affinity of α6 for β1, particularly when the GFFKR sequence is absent. Although the GFFKR motif is not essential for association of α6 with β4, it increases the stability of the α6β4 integrin. The cytoplasmic domain of α6 is essential for inside‐out and outside‐in signaling via the α6β1 receptor, but not for adhesion via α6β4. We show that α6β4 is a constitutively active receptor. Thus, unlike adhesion by most other integrins, adhesion by α6β4 does not seem to depend on any active cellular process. Binding of α6β4 to ligand was only slightly affected by truncation of the α6 cytoplasmic domain N‐terminal to the GFFKR sequence and became partially dependent on metabolic energy. These data indicate that truncations of the cytoplasmic domain of the α6 subunit affect the assembly and function of α6β1 more strongly than those of α6β4. This difference may be due to the greater affinity of α6 for β4 than for β1, which makes α6β4 less susceptible to the effect of truncations.