Figure 4.
Fig. 4. Model of adhesion-regulated RPTPµ signaling.
Cadherins [ectodomains shown in orange, PDB entry 1L3W (29)]
establish intercellular contacts via trans interactions, as well
as cis interactions (black arrow) (2, 29). RPTPµ (shown in
blue) trans interactions are pH sensitive (8, 18), which is
consistent with the polar nature of the interface, and therefore
cannot form at the low pH of the secretory pathway. Cell surface
RPTPµ molecules rapidly recirculate, unless there is an
appropriate recognition match (5). Trans RPTPµ
dimerization may be complemented by weak interactions in cis
(black arrow and question mark) (8, 15). RPTPµ can
stabilize the cadherin-catenin complex [drawn schematically:
-catenin (yellow
circles), ß-catenin (light green ovals), and p120-catenin
(dark green ovals)] by dephosphorylation (3)(red arrows). Type
IIB RPTPs are processed in multiple proteolytic steps (5, 13,
14). Protein convertases (in the trans-Golgi network) nick the
FN4 domain (13, 14), potentially contributing flexibility. ADAM
10 cleaves close to the membrane (thick gray lines), causing the
shedding of RPTPµ (5, 14) and cadherin (36) ectodomains.
Subsequent -secretase–dependent
intramembrane cleavage releases the RPTPµ intracellular
region (blue ovals) (14). The cadherin and RPTPµ
ectodomains (crystal structures drawn to the same scale) are
shown perpendicular to the cell surface to simplify the figure.
EM analysis of adherens junctions and desmosomes has revealed
the possibility of non-orthogonal orientations with respect to
the membrane surface [with variable tilt angles (28, 31)], but
it is not clear to what extent this is caused by sample
preparation procedures or flexibility of the juxtamembrane
regions.
The above figure is reprinted
by permission from the AAAs:
Science
(2007,
317,
1217-1220)
copyright 2007.
-catenin (yellow
circles), ß-catenin (light green ovals), and p120-catenin
(dark green ovals)] by dephosphorylation (3)(red arrows). Type
IIB RPTPs are processed in multiple proteolytic steps (5, 13,
14). Protein convertases (in the trans-Golgi network) nick the
FN4 domain (13, 14), potentially contributing flexibility. ADAM
10 cleaves close to the membrane (thick gray lines), causing the
shedding of RPTPµ (5, 14) and cadherin (36) ectodomains.
Subsequent 
-secretase–dependent
intramembrane cleavage releases the RPTPµ intracellular
region (blue ovals) (14). The cadherin and RPTPµ
ectodomains (crystal structures drawn to the same scale) are
shown perpendicular to the cell surface to simplify the figure.
EM analysis of adherens junctions and desmosomes has revealed
the possibility of non-orthogonal orientations with respect to
the membrane surface [with variable tilt angles (28, 31)], but
it is not clear to what extent this is caused by sample
preparation procedures or flexibility of the juxtamembrane
regions.