E-cadherin. LGN can directly interact with the cytosolic tail of
E-cadherin that localizes LGN at the cell–cell contacts
[117]. Increase in tension does not trigger a polarized distribution
of E-cadherin, while LGN and myosin IIA are polarized suggesting
that an additional intermediate, LGN interacting protein might be
involved in its polarized localization. This protein could be SCRIBBLE as other ones (DLG, Afadin, ERM proteins) were ruled out in
this study. SCRIBBLE is indeed able to interact with LGN, and the
interaction between LGN and E-cadherin is reduced in cells
depleted for SCRIBBLE. The formation of this ternary complex
is also important for proper cell division [101]. Taken together, all
these data point to SCRIBBLE as a likely “second line” mechanotransducer to trigger signaling pathways downstream of the
mechanosensitive E-cadherin units.
5 Concluding Remarks
In the last two decades, mechanical stimuli have emerged as essential regulators of several biological processes. Mechanotransduction
has revealed a new layer of control of the interaction between
proteins, and will potentially lead to global guiding principles for
the organization of complex living systems. The convergent interests from physicists and biologists to understand the complexity of
integrated systems have led to the development of new biophysical
tools. These new technological advances such as stretching devices,
optical/magnetic tweezers, or atomic force microscopy have
enabled to measure and apply controlled forces on cells. Applying
different forces on cells trigger several cellular responses and activate different signaling pathways that have led to the identification
of an emerging mechanotransducing function for PDZ proteins.
These mechanotransducers can participate in mechanoreception
and mechanotransmission as direct mechanosensitive components
or as second line mechanotransducers.
Pulling forces generated by the actomyosin network can stretch
molecules exposing their cryptic binding sites or cryptic phosphorylation sites, triggering specific signaling pathways [5, 118]. In the
case of ZO1, physical forces are responsible for the stretching of the
molecule that is needed for its correct localization while allowing
for the interaction with its different partners. This activated
unfolded ZO1 protein is important for the maintenance of the
TJs. The actomyosin network can thus directly by its contractions
pull on proteins but also on the actin cytoskeleton, resulting in flow
of material that leads to the formation of polarized clusters of
proteins at the cell cortex that allow for adaptation of cell cytoskeleton [51, 119]. Under higher cortical tension PAR3 clusters and
MUPP1 is recruited to the cell cortex. The tension-dependent
clustering of PAR3 could promote its oligomerization at the cell
268
Elsa Bazellie ` res and Andre ´ Le Bivic
E-cadherin that localizes LGN at the cell–cell contacts
[117]. Increase in tension does not trigger a polarized distribution
of E-cadherin, while LGN and myosin IIA are polarized suggesting
that an additional intermediate, LGN interacting protein might be
involved in its polarized localization. This protein could be SCRIBBLE as other ones (DLG, Afadin, ERM proteins) were ruled out in
this study. SCRIBBLE is indeed able to interact with LGN, and the
interaction between LGN and E-cadherin is reduced in cells
depleted for SCRIBBLE. The formation of this ternary complex
is also important for proper cell division [101]. Taken together, all
these data point to SCRIBBLE as a likely “second line” mechanotransducer to trigger signaling pathways downstream of the
mechanosensitive E-cadherin units.
5 Concluding Remarks
In the last two decades, mechanical stimuli have emerged as essential regulators of several biological processes. Mechanotransduction
has revealed a new layer of control of the interaction between
proteins, and will potentially lead to global guiding principles for
the organization of complex living systems. The convergent interests from physicists and biologists to understand the complexity of
integrated systems have led to the development of new biophysical
tools. These new technological advances such as stretching devices,
optical/magnetic tweezers, or atomic force microscopy have
enabled to measure and apply controlled forces on cells. Applying
different forces on cells trigger several cellular responses and activate different signaling pathways that have led to the identification
of an emerging mechanotransducing function for PDZ proteins.
These mechanotransducers can participate in mechanoreception
and mechanotransmission as direct mechanosensitive components
or as second line mechanotransducers.
Pulling forces generated by the actomyosin network can stretch
molecules exposing their cryptic binding sites or cryptic phosphorylation sites, triggering specific signaling pathways [5, 118]. In the
case of ZO1, physical forces are responsible for the stretching of the
molecule that is needed for its correct localization while allowing
for the interaction with its different partners. This activated
unfolded ZO1 protein is important for the maintenance of the
TJs. The actomyosin network can thus directly by its contractions
pull on proteins but also on the actin cytoskeleton, resulting in flow
of material that leads to the formation of polarized clusters of
proteins at the cell cortex that allow for adaptation of cell cytoskeleton [51, 119]. Under higher cortical tension PAR3 clusters and
MUPP1 is recruited to the cell cortex. The tension-dependent
clustering of PAR3 could promote its oligomerization at the cell
268
Elsa Bazellie ` res and Andre ´ Le Bivic