The alpha6 integrin subunit participates in the formation of both alpha6 beta1 and alpha6 beta4 laminin receptors, which have
been reported to play an important role in cell adhesion and migration and in morphogenesis.
NCBI Summary:
The ITGA6 protein product is the integrin alpha chain alpha 6. Integrins are integral cell-surface proteins composed of an alpha chain and a beta chain. A given chain may combine with multiple partners resulting in different integrins. For example, alpha 6 may combine with beta 4 in the integrin referred to as TSP180, or with beta 1 in the integrin VLA-6. Integrins are known to participate in cell adhesion as well as cell-surface mediated signalling.
The physiological role(s) of integrins was
investigated by Fujiwara H et al using in vitro human granulosa cell culture and in vivo mouse ovulation model. In human luteinizing granulosa
cell culture obtained from patients, laminin, which is a ligand for integrin alpha
6 beta 1, suppressed the production of progesterone by granulosa cells. On the other hand, the anti-alpha 6 monoclonal
antibody (mAb) GoH3, which partially inhibits the interaction between integrin alpha 6 beta 1 and laminin, enhanced
production of progesterone by 2-fold of the control under the culture with laminin, indicating that integrin alpha 6 beta 1
regulates the luteinization of human granulosa cell during the periovulatory phase. In an immature superovulated 13-day-old
ICR (CD-1) mice model, intraperitoneal administration of GoH3 induced successful ovulation, showing that integrin alpha 6 beta 1 is related to gonadotropin-induced follicular
growth.
DNA fragmentation (apoptosis) was studied during the follicular, periovulatory and luteal phase in the marmoset monkey
ovary by means of terminal transferase mediated in situ nick end labeling, and correlated with immunohistochemical
localization of integrins (beta 1, alpha 2 and alpha 6 subunits). Giebel J reported staining intensities for integrins beta 1 and alpha 6 were strong in intact primordial/primary, secondary and tertiary follicles. Integrin expression of granulosa cells was weak in atretic tertiary
follicles but not in atretic primary or secondary follicles. Double labeling revealed that DNA fragmentation was solely found
in granulosa cells of tertiary follicles displaying faint or absent staining for both integrin subunits. During the periovulatory
and the luteal phase, granulosa cells of atretic tertiary follicles bordering on the basal membrane, which were referred to as
luteinizing cells, expressed the beta 1 subunit as well as the alpha 2-integrin subunit whereas granulosa cells neighboring to
the antrum were apoptotic and negative for integrin immunoreactivity.
Fujiwara H, et al. reported that laminin suppresses progesterone production by human luteinizing granulosa cells via interaction with integrin alpha 6 beta 1. The sperm antigen fertilin alpha/beta and the integrin complex alpha6beta1 present on the oolemma are two of the most
promising candidates to mediate gamete interaction. During growth, the plasma membrane of both hamster and mouse
zona-free oocytes acquires the capacity to fuse with acrosome-reacted sperm when oocytes reach the size of 25-30 microm in
diameter, suggesting changes in the membrane molecular composition. Zuccotti M et al
found that both alpha6 and beta1 genes are
expressed in female germ cells during all the stages of development analyzed, from 10.5 to 18.5 d.p. c., during oocyte
growth, and in ovulated eggs.
Expression regulated by
Comment
Ovarian localization
Oocyte, Cumulus, Granulosa, Theca, Luteal cells
Comment
Fujiwara H et al reported that immunohistochemical study showed that integrin alpha 6 was highly expressed on granulosa cells in
preovulatory follicles in the human ovary, whereas it was highly expressed on granulosa cells in small follicles in the
porcine ovary. As a common characteristic of integrin alpha 6 expression in both ovaries, granulosa cells located in inner
layers, which are not in contact with the basal lamina, expressed integrin alpha 6 on the cell surface.
Frojdman K et al reported that reorganization of the gonadal cords into follicles at birth was accompanied with strong and uniform
re-expression of the alpha 6 subunit on the surface of the cord cells. Vascular endothelial cells and the cells of the postnatal
surface epithelium remained positive for the alpha 6 integrin subunit. In larger follicles, the intensity of the reaction for the
integrin subunit varied. The theca cells of growing follicles contained the alpha 6 subunit. The results show that this subunit
of integrins is present in phases of increased adhesion and aggregation, and that its expression probably is involved in the
regulation of ovarian epithelial differentiation.
Follicle stages
Primary, Secondary, Antral, Preovulatory, Corpus luteum
Comment
Integrins were localized immunohistochemically in marmoset ovaries (Callithrix jacchus) of defined cycle stages by Giebel J et al . With
monoclonal antibodies against beta 1, alpha 2, alpha 3, and alpha 6 integrin subunits, immunoreactivity was predominantly
found in ovaries of the follicular phase. In the luteal phase, non-luteal cells, e.g. fibroblasts or endothelial cells expressed
beta 1, alpha 2, or alpha 6 integrins. Immunostaining for the beta 1 subunit was strongest in granulosa cells of all growing
follicles. Weak immunoreactivity was found in granulosa cells of atretic follicles, theca and interstitial cells. With the alpha
2 antibody, binding was evident in granulosa cells of many, but not of all, primordial and primary follicles. Expression of
alpha 2 was also found in luteinized granulosa cells of tertiary follicles. In growing follicles, immunoreactivity of alpha 3
was restricted to granulosa cells of early secondary follicles. Within the epithelium, staining was almost exclusively found in
granulosa cells bordering on the basal granulosa cell layer. In advanced stages of atresia, granulosa cells of antral follicles
expressed the alpha 3 subunit. Integrin alpha 6 expression was evident in granulosa cells of all growing follicles but was
absent during advanced stages of degeneration.
Phenotypes
Mutations
1 mutations
Species: mouse
Mutation name: None
type: null mutation fertility: embryonic lethal Comment:Georges-Labouesse et al. (1996) produced mice that were deficient in alpha-6 integrin through a targeted disruption of the
alpha-6 integrin gene. They reported that these mice developed normally before birth but died shortly thereafter with severe
blistering of the skin and other epithelia.