Biology Reference
In-Depth Information
9.2.2 Tropoelastin/Elastin
Tropoelastin is the monomer that composes elastin, arising from one gene in all
species. The sequence includes several exons and introns, which allows for multiple
mRNA splice variants within the same organ. Additionally, there may be different
splice variants produced in adulthood versus development resulting in different
isoforms as a function of age (Rosenbloom et al.
1993
).
Tropoelastin, a ~70-kDa monomer composed of alternating hydrophobic and
lysine domains (Gray et al.
1973
), is produced by fibroblasts and smooth muscle
cells (Pasquali-Ronchetti and Baccarani-Contri
1997
). These lysine residues are
cross linked by lox family enzymes to other tropoelastin fibers to form elastin
(Lucero and Kagan
2006
). Of the approximately 40 residues, all but ~2-5 are cross-
linked. It is this degree of cross-linking that gives elastin its stability and insolubil-
ity (Wagenseil and Mecham
2007
). A hypothesized model of elastic fiber assembly
is discussed below.
Elastin-deficient (
Eln
/
) mice display mortality within a few days of birth,
which is due to vascular obstruction from smooth muscle cell overproliferation and
disarrangement (Li et al.
1998a
,
b
).
Eln
+/
mice, however, have a normal life span
but are hypertensive with smaller blood vessels. Surprisingly, they have increased
layers of elastin associated with smooth muscle (lamellar units) (Li et al.
1998a
,
b
;
Faury et al.
2003
). Recent data looking at aortic development in mice show that these
changes in structure occur in the few days before birth (E18) to birth (P0), as pressure
and blood flow through the vessel increases (Wagenseil and Mecham
2007
).
9.2.3 Fibrillins
The microfibrils that compose the elastic fiber are largely composed of fibrillins
(Sakai et al.
1991
). These are large (~350 kDa) cysteine-rich glycoproteins with
calcium binding epidermal growth factor (EGF)-like domains that provide the
majority of the structure. There are currently three fibrillins in humans that have
been identified (Fib1, -2, and -3) although, in mice, the third fibrillin has been
disrupted due to chromosomal rearrangement (Corson et al.
2004
; Kielty
2006
).
Fibrillin-1 and -2 are known to bind tropoelastin in solid phase binding assays
(Trask et al.
2000a
,
b
). They are expressed in similar organs in mice but with some
regional and quantitative differences. In addition, fibrillin-2 is expressed earlier in
development (Zhang et al.
1995
). These proteins are produced by fibroblasts and
contain conserved Arg-Gly-Asp (RGD) sequences that interact with integrins
(Sakamoto et al.
1996
; Bax et al.
2003
). In addition they have heparin binding
domains that interact with cell surface heparin sulfate proteoglycans (Tiedemann
et al.
2001
; Ritty et al.
2003
). These interactions may be essential to guiding in vivo
assembly and may also serve as a signal to cells. In fact, the addition of heparin to
cell cultures prevented the assembly of microfibrils (Tiedemann et al.
2001
).
