Km. Guan et al., Expression and cellular distribution of alpha(v) integrins in beta(1) integrin-deficient embryonic stem cell-derived cardiac cells, J MOL CEL C, 33(3), 2001, pp. 521-532
beta (1) integrin-deficient (beta (1) (-/-)) ES cells showed increased diff
erentiation of cardiac cells characterized by reduced adhesion and high bea
ting frequency. Whereas in whole embryoid body outgrowths of beta (-/-)(1)
cells maximum levels of alpha (w), beta (3), and beta (5), integrin mRNA we
re delayed and transiently upregulated, in cardiac clusters isolated from b
eta (-/-)(1) cells, only beta (3) intesrin mRNA levels were enhanced in com
parison to wild-type (wt) cells. To answer the question, whether alpha (v)
and beta (3) integrins may compensate, at least partially. the loss of beta
(3), integrin function during cardiac differentiation, the distribution of
alpha (v) and beta (3), integrins in beta (-/-)(1) and wt pacemaker-like c
ardiac cells was analyzed. A different distribution of alpha (v) and beta (
3), integrins in beta (-/-)(1) v wt cardiac cells was found. In wt cardiac
cells, beta (1) integrin was localized in specialized subsarcolemmal region
s, in particular, at focal contacts and costameres, but alpha (v) integrin
was diffusely distributed. In contrast, in beta (-/-)(1) cardiac cells, alp
ha (v) integrin was preponderantly localized at cell membranes, focal conta
cts and costameres. beta (3), integrin displayed a diffuse pattern both in
wt and in beta (-/-)(1) pacemaker-like cells at early differentiation stage
s, whereas at terminal stages. beta (3), was colocalized with sarcomeres in
wt, but not in beta (-/-)(1) pacemaker-like cells. Quantitative immunofluo
rescence analysis revealed increased alpha (v) and beta (3) integrin levels
in beta (-/-)(1) pacemaker-like cardiac cells. Our results led us to concl
ude that altered cellular distribution of alpha (v) integrin and upregulati
on of beta (3), integrin correlate with growth and survival of beta (-/-)(1
) cardiac pacemaker-like cells at an early developmental state. However, al
pha (v) and beta (3) integrins cannot Functionally compensate the loss of b
eta (1), integrin during terminal differentiation of cardiac cells implicat
ing that cardiomyocytes require specific beta (1) integrin functions for ca
rdiac specialization. (C) 2001 Academic Press.