cortex where it could recruit PAR6 and aPKC, leading to the
establishment of anteroposterior or apicobasal polarity. The recruitment of the PDZ protein MUPP1 to the TJs is key to maintaining
the integrity of the TJ barrier during hyperosmotic stress. Finally,
loading forces can regulate cell adhesion machineries [105, 106,
120]. The adhesive contacts can adapt to external forces, by modifying their binding to specific proteins, their structural conformations, their stability but also their links to the actin cytoskeleton.
Some PDZ proteins such as SCRIBBLE, Afadin, or ZO1 can, upon
loading forces, strengthen the cell adhesion machinery at the ZA
and TJs localization respectively to preserve epithelial homeostasis
by allowing for the proper polarization of the tissue and the tethering of the adhesions to the actin cytoskeleton. In these cases, the
connections between adhesions are strengthened by assembly of
new components, however in other cases the connections can be
severed [121]. DLG is located at cell–cell contacts and upon forces
generation will recruit aPKC at the ZA. The recruitment of aPKC
by DLG at the ZA can then regulate the load of tension at the cell–
cell contact by controlling the depolymerization of actin and disruption of cell–cell contact leading to a relaxation of the tissue
when the forces are too elevated.
The active nature of cell adhesion machineries implies that the
time from the mechanosensing to the mechanoresponse is slow and
occurs within seconds to minutes allowing the occurrence of many
different interactions between proteins [122–124]. In the case of
PDZ scaffolds proteins, this could trigger specific interactions
allowing for the cells to have a multimodal adaptive “repertoire”
to properly adapt their responses to the change in forces.
Acknowledgments
Elsa Bazellie `res and Andre ´ Le Bivic are supported by CNRS. This
project was developed in the context of the LabEx INFORM
(ANR-11-LABX-0054) and of the A*MIDEX project (ANR-11IDEX-0001-02) funded by the “Investissements d’Avenir” French
Government program.
References
1. Petridou NI, Heisenberg C (2019) Tissue
rheology in embryonic organization. EMBO
J 38:e102497
2. Salvi AM, DeMali KA (2018) Mechanisms
linking mechanotransduction and cell metabolism. Curr Opin Cell Biol 54:114–120
3. Jaalouk DE, Lammerding J (2009) Mechanotransduction gone awry. Nat Rev Mol Cell
Biol 10:63–73
4. Sidhwani P, Yelon D (2019) Fluid forces
shape the embryonic heart: insights from zebrafish. Curr Top Dev Biol 132:395–416
5. Pruitt BL, Dunn AR, Weis WI, Nelson WJ
(2014) Mechano-transduction: from molecules to tissues. PLoS Biol 12:e1001996
6. Dzamba BJ, DeSimone DW (2018) Extracellular matrix (ECM) and the sculpting of
Mechanoregulation of PDZ Proteins
269
establishment of anteroposterior or apicobasal polarity. The recruitment of the PDZ protein MUPP1 to the TJs is key to maintaining
the integrity of the TJ barrier during hyperosmotic stress. Finally,
loading forces can regulate cell adhesion machineries [105, 106,
120]. The adhesive contacts can adapt to external forces, by modifying their binding to specific proteins, their structural conformations, their stability but also their links to the actin cytoskeleton.
Some PDZ proteins such as SCRIBBLE, Afadin, or ZO1 can, upon
loading forces, strengthen the cell adhesion machinery at the ZA
and TJs localization respectively to preserve epithelial homeostasis
by allowing for the proper polarization of the tissue and the tethering of the adhesions to the actin cytoskeleton. In these cases, the
connections between adhesions are strengthened by assembly of
new components, however in other cases the connections can be
severed [121]. DLG is located at cell–cell contacts and upon forces
generation will recruit aPKC at the ZA. The recruitment of aPKC
by DLG at the ZA can then regulate the load of tension at the cell–
cell contact by controlling the depolymerization of actin and disruption of cell–cell contact leading to a relaxation of the tissue
when the forces are too elevated.
The active nature of cell adhesion machineries implies that the
time from the mechanosensing to the mechanoresponse is slow and
occurs within seconds to minutes allowing the occurrence of many
different interactions between proteins [122–124]. In the case of
PDZ scaffolds proteins, this could trigger specific interactions
allowing for the cells to have a multimodal adaptive “repertoire”
to properly adapt their responses to the change in forces.
Acknowledgments
Elsa Bazellie `res and Andre ´ Le Bivic are supported by CNRS. This
project was developed in the context of the LabEx INFORM
(ANR-11-LABX-0054) and of the A*MIDEX project (ANR-11IDEX-0001-02) funded by the “Investissements d’Avenir” French
Government program.
References
1. Petridou NI, Heisenberg C (2019) Tissue
rheology in embryonic organization. EMBO
J 38:e102497
2. Salvi AM, DeMali KA (2018) Mechanisms
linking mechanotransduction and cell metabolism. Curr Opin Cell Biol 54:114–120
3. Jaalouk DE, Lammerding J (2009) Mechanotransduction gone awry. Nat Rev Mol Cell
Biol 10:63–73
4. Sidhwani P, Yelon D (2019) Fluid forces
shape the embryonic heart: insights from zebrafish. Curr Top Dev Biol 132:395–416
5. Pruitt BL, Dunn AR, Weis WI, Nelson WJ
(2014) Mechano-transduction: from molecules to tissues. PLoS Biol 12:e1001996
6. Dzamba BJ, DeSimone DW (2018) Extracellular matrix (ECM) and the sculpting of
Mechanoregulation of PDZ Proteins
269