J. Evan Sadler talks with
ScienceWatch.com and answers a few questions
about this month's Fast Moving Front in the field of
Clinical Medicine. The author has also sent along
images of their work.
Article: Update on the pathophysiology and
classification of von Willebrand disease: a report of
the Subcommittee on von Willebrand
Factor
Authors: Sadler, JE, et. al
J THROMB HAEMOST, 4 (10): 2103-2114 OCT 2006
Figure 1: Biosynthesis of VWF. The
VWF precursor is translocated into the ER,
where the signal peptide (SP) is cleaved
and disulfide bonds form between C-terminal
domains to yield proVWF dimers. In the
Golgi, disulfide bonds form between
N-terminal domains to yield multimers, and
the propeptide is cleaved. Multimers are
secreted or packaged into Weibel-Palade
bodies for later secretion.
Figure 2:
Figure 2: Classification of VWD.
Figure 3:
Figure 3: Mutations in VWD type 2. The VWF
precursor consists of a signal peptide
(residues 1-22), propeptide (residues
23-763), and mature subunit residues
764-2813. Structural motifs are labeled.
Locations are indicated for intersubunit
disulfide bonds (S-S); binding sites for
factor VIII, platelet GPIb, fibrillar
collagen, platelet integrin aIIbß3;
and the site cleaved by the metalloprotease
ADAMTS13. Circles show the location of
mutations known to cause VWD type 2A
(orange), 2B (blue), 2M (yellow), and 2N
(white).