Biology Reference
In-Depth Information
In humans, mutations in fibrillin-1 leads to Marfan's syndrome, while fibrillin-2
mutations cause congenital contractural arachnodactyly (Lee et al.
1991
).
Fbn1
/
mice die within 2 weeks of birth secondary to pulmonary and cardiac complications
including diaphragmatic collapse, enlarged airspaces, and ruptured aortic aneurysms
(Carta et al.
2006
).
Fbn2
/
mice develop syndactyly but otherwise have a normal
life span without pulmonary or vascular defects (Chaudhry et al.
2001
; Carta et al.
2006
). Mice deficient in both Fbn1 and Fbn2 die in utero with minimal elastic fibers
between smooth muscle layers without organization (Carta et al.
2006
).
9.2.4 Microfibrillar-Associated Glycoproteins (MAGP1 and -2)
MAGP1 (
Mfap
) and MAGP2 (
Mfap5
) are small (~20 kDa) glycoproteins localized
to beaded areas of the microfibrils (Henderson et al.
1996
; Wagenseil and Mecham
2007
). MAGP1 is the only protein besides the fibrillins that is constitutively part of
the microfibril (Gibson et al.
1986
). It binds fibrillin-1, -2, and tropoelastin (Brown-
Augsburger et al.
1994
; Trask et al.
2000a
,
b
; Jensen et al.
2001
). It has therefore
traditionally been considered an important component in elastic fiber assembly
by serving as an intermediate between fibrillin and tropoelastin. However, mice
deficient in MAGP1 (
Mfap2
/
) do not have structural abnormalities in elastin,
although they have a tendency for bleeding and altered wound healing. Thus it
appears that MAGP1 is not essential in elastic fiber formation. Interestingly,
MAGP1 binds TGF-
and BPM-7 suggesting that it may modulate microfibril-
mediated growth factor signaling (Weinbaum et al.
2008
). MAGP2 is found in most
microfibrils and binds fibrillin-1 and -2 (Penner et al.
2002
). It possesses an RGD
cell recognition motif with which it binds integrins. MAGP2-deficient mice have
not been described. However, its restricted pattern of localization and expression
suggest that it may be more important in cell signaling (Kielty et al.
2005
).
b
9.2.5 Key Associated Proteins
There are additional proteins associated with elastic fibers, including the fibulins,
latent TGF-
b
-binding proteins (LTBPs), and elastin microfibril interface located
proteins (EMILINs). These components contribute to the structural and bioactive
properties of mature elastic fibers. They have recently been reviewed in detail
(Kielty
2006
; Wagenseil and Mecham
2007
).
9.2.6 Elastic Fiber Assembly
Microfibril assembly is beyond the scope of this review. Suffice it to say that there
are complex modifications and trafficking of fibrillin along with interactions with
