Integrin α6β4E variant is associated with actin and CD9 structures and modifies the biophysical properties of cell-cell and cell-extracellular matrix interactions
Hinton, James P
Gard, Jaime M C
Garcia, Joe G N
Knudsen, Beatrice S
Nagle, Raymond B
Cress, Anne E
AffiliationUniv Arizona, Canc Biol Res Program
Univ Arizona, Dept Med
Univ Arizona, Dept Pathol
Univ Arizona, Dept Cellular & Mol Med
Univ Arizona, Univ Arizona Canc Ctr
MetadataShow full item record
PublisherAMER SOC CELL BIOLOGY
CitationWang, M., Hinton, J. P., Gard, J. M., Garcia, J. G., Knudsen, B. S., Nagle, R. B., & Cress, A. E. (2019). Integrin α6β4E variant is associated with actin and CD9 structures and modifies the biophysical properties of cell–cell and cell–extracellular matrix interactions. Molecular biology of the cell, 30(7), 838-850.
JournalMOLECULAR BIOLOGY OF THE CELL
Rights© 2019 Wang et al. This article is distributed by The American Society for Cell Biology under license from the author(s). Two months after publication it is available to the public under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License.
Collection InformationThis item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at email@example.com.
AbstractIntegrin alpha 6 beta 4 is an essential, dynamic adhesion receptor for laminin 332 found on epithelial cells, required for formation of strong cell-extracellular matrix (ECM) adhesion and induced migration, and coordinated by regions of the beta 4C cytoplasmic domain. beta 4E, a unique splice variant of beta 4 expressed in normal tissue, contains a cytoplasmic domain of 231 amino acids with a unique sequence of 114 amino acids instead of beta 4C's canonical 1089 amino acids. We determined the distribution of alpha 6 beta 4E within normal human glandular epithelium and its regulation and effect on cellular biophysical properties. Canonical alpha 6 beta 4C expressed in all basal cells, as expected, while alpha 6 beta 4E expressed within a subset of luminal cells. alpha 6 beta 4E expression was induced by three-dimensional culture conditions, activated Src, was reversible, and was stabilized by bortezomib, a proteasome inhibitor. alpha 6 beta 4C expressed in all cells during induced migration, whereas alpha 6 beta 4E was restricted to a subset of cells with increased kinetics of cell-cell and cell-ECM resistance properties. Interestingly, alpha 6 beta 4E presented in "ringlike" patterns measuring similar to 1.75 x 0.72 microns and containing actin and CD9 at cell-ECM locations. In contrast, alpha 6 beta 4C expressed only within hemidesmosome-like structures containing BP180. Integrin alpha 6 beta 4E is an inducible adhesion isoform in normal epithelial cells that can alter biophysical properties of cell-cell and cell-ECM interactions.
VersionFinal published version
SponsorsNational Institutes of Health, National Cancer Institute (NIH-NCI) [RO1CA159406]; NIH-NCI [T32CA009213]; NIH, National Heart, Lung, and Blood Institute [P01 HL126609]; Tim and Diane Bowden Fellowship in Cancer Biology; [P30 CA23074]
- A recombinant tail-less integrin beta 4 subunit disrupts hemidesmosomes, but does not suppress alpha 6 beta 4-mediated cell adhesion to laminins.
- Authors: Spinardi L, Einheber S, Cullen T, Milner TA, Giancotti FG
- Issue date: 1995 Apr
- Dynamics of the alpha6beta4 integrin in keratinocytes.
- Authors: Geuijen CA, Sonnenberg A
- Issue date: 2002 Nov
- Formation of hemidesmosomes in cells of a transformed murine mammary tumor cell line and mechanisms involved in adherence of these cells to laminin and kalinin.
- Authors: Sonnenberg A, de Melker AA, Martinez de Velasco AM, Janssen H, Calafat J, Niessen CM
- Issue date: 1993 Dec
- Endothelial cells assemble two distinct alpha6beta4-containing vimentin-associated structures: roles for ligand binding and the beta4 cytoplasmic tail.
- Authors: Homan SM, Mercurio AM, LaFlamme SE
- Issue date: 1998 Sep
- The integrin alpha6beta4 functions in carcinoma cell migration on laminin-1 by mediating the formation and stabilization of actin-containing motility structures.
- Authors: Rabinovitz I, Mercurio AM
- Issue date: 1997 Dec 29