polymerization causes a reduction of the PAR3 clusters on the
cortex, demonstrating that higher cortical tension can drive
PAR3 cluster formation at the cortex [50]. The actomyosin membrane associated network generates flows [51], which promote
symmetry breaking along the anterior posterior axis through the
advection of polarity components [52–54]. The polarized actomyosin contractions pull actin networks along the membrane toward
the anterior region while triggering local disassembly and turnover
via increased local tension, resulting in flow of material [55]. Based
on the advective flow model proposed by Goerhing et al. [53] that
predicts that diffusivity and turnover of cortical polarity proteins
should be slow and stable enough to be passively transport by the
advective cortical flow, Wang et al. [50] postulate a “clustering and
stabilization” hypothesis for PAR3. By using fluorescence recovery
after photobleaching, they demonstrate that the half-life of PAR3
and PKC are shorter before symmetry breaking. During the early to
middle establishment phase, when the clusters are formed, the halflife increases. Molecularly, during this phase the activity of Cdc42 is
reduced allowing PKC3 and PAR6 to associate with PAR3 clusters
at the cortex and thus facilitates effective transport by advective
cortical flows. During the maintenance phase, the half-lives of
PAR3 and PKC are shorter, when the clusters disassemble, concomitant with an increased activity of Cdc42 that prevents PKC and
PAR6 association with PAR3. As cortical tensions trigger a dynamic
equilibrium between an unclustered and clustered form of PAR3
correlating with its association with PAR6 and PKC, it is tempting
to speculate that PAR3 may undergo structural changes by
mechanical stretching, which could relieve the amino-terminal
CR1 domain from intramolecular inhibitions, thus promoting
PAR3 oligomerization [56]. These mechanically induced conformational changes may directly activate the ability of the CR1
domain to facilitate its oligomerization, and proper localization in
cells [56]. Furthermore, similar cortical flows are observed during
cell division or cell migration, and then could, if proven, also
explain the interaction between the different members of the PAR
complex.
4 PDZ Proteins “Second Line” Mechanotransducers
In this part, we will describe how some PDZ proteins interact with
proteins that are activated upon forces. These interactions may
trigger a change in the conformation or in the localization of the
“second line” mechanotransducers, thereby regulating different
signal pathways.
Mechanoregulation of PDZ Proteins
263
cortex, demonstrating that higher cortical tension can drive
PAR3 cluster formation at the cortex [50]. The actomyosin membrane associated network generates flows [51], which promote
symmetry breaking along the anterior posterior axis through the
advection of polarity components [52–54]. The polarized actomyosin contractions pull actin networks along the membrane toward
the anterior region while triggering local disassembly and turnover
via increased local tension, resulting in flow of material [55]. Based
on the advective flow model proposed by Goerhing et al. [53] that
predicts that diffusivity and turnover of cortical polarity proteins
should be slow and stable enough to be passively transport by the
advective cortical flow, Wang et al. [50] postulate a “clustering and
stabilization” hypothesis for PAR3. By using fluorescence recovery
after photobleaching, they demonstrate that the half-life of PAR3
and PKC are shorter before symmetry breaking. During the early to
middle establishment phase, when the clusters are formed, the halflife increases. Molecularly, during this phase the activity of Cdc42 is
reduced allowing PKC3 and PAR6 to associate with PAR3 clusters
at the cortex and thus facilitates effective transport by advective
cortical flows. During the maintenance phase, the half-lives of
PAR3 and PKC are shorter, when the clusters disassemble, concomitant with an increased activity of Cdc42 that prevents PKC and
PAR6 association with PAR3. As cortical tensions trigger a dynamic
equilibrium between an unclustered and clustered form of PAR3
correlating with its association with PAR6 and PKC, it is tempting
to speculate that PAR3 may undergo structural changes by
mechanical stretching, which could relieve the amino-terminal
CR1 domain from intramolecular inhibitions, thus promoting
PAR3 oligomerization [56]. These mechanically induced conformational changes may directly activate the ability of the CR1
domain to facilitate its oligomerization, and proper localization in
cells [56]. Furthermore, similar cortical flows are observed during
cell division or cell migration, and then could, if proven, also
explain the interaction between the different members of the PAR
complex.
4 PDZ Proteins “Second Line” Mechanotransducers
In this part, we will describe how some PDZ proteins interact with
proteins that are activated upon forces. These interactions may
trigger a change in the conformation or in the localization of the
“second line” mechanotransducers, thereby regulating different
signal pathways.
Mechanoregulation of PDZ Proteins
263