Chapter 15
Mechanoregulation of PDZ Proteins, An Emerging Function
Elsa Bazellie ` res and Andre ´ Le Bivic
Abstract
Mechanical forces have emerged as essential regulators of cell organization, proliferation, migration, and
polarity to regulate cellular and tissue homeostasis. Changes in forces or loss of the cellular response to them
can result in abnormal embryonic development and diseases. Over the past two decades, many efforts have
been put in deciphering the molecular mechanisms that convert forces into biochemical signals, allowing
for the identification of many mechanotransducer proteins. Here we discuss how PDZ proteins are
emerging as new mechanotransducer proteins by altering their conformations or localizations upon force
loads, leading to the formation of macromolecular modules tethering the cell membrane to the actin
cytoskeleton.
Key words PDZ proteins, Forces, Tight junctions, Adherens junctions, Actomyosin
1 A Brief Introduction on Mechanotransduction/Mechanoregulation in Biology
All the cells and tissues of the body are subject to external and
internal forces. These forces can affect the shape and intracellular
organization of cells, their proliferation, their migration, and their
intercellular interactions. Forces influence the development of
embryos [1] as well as cell functions and homeostasis in the adult
[2]. Moreover, many disease states are characterized by changes in
these forces and/or a loss of the normal cellular response to them
[3]. Over the last decade, mechanotransduction has emerged as a
key process in development and diseases. Mechanotransduction can
be defined as a cellular event that converts a mechanical input such
as fluid shear stress (blood vessels), stretch (lung, intestine),
osmotic forces (urinary tract), mechanical load (bone, muscle)
[4, 5] as well as the impact of the stiffness of the extracellular matrix
(ECM) that surrounds most cells leading to a biochemical response
[6]. In well-studied examples of mechanotransduction, proteins
can undergo force-induced changes into conformations that lead
to modification in affinity for binding partners or catalytic activity.
The mechanical load triggers biochemical changes that can
Jean-Paul Borg (ed.), PDZ Mediated Interactions: Methods and Protocols, Methods in Molecular Biology, vol. 2256,
https://doi.org/10.1007/978-1-0716-1166-1_15, © Springer Science+Business Media, LLC, part of Springer Nature 2021
257
Mechanoregulation of PDZ Proteins, An Emerging Function
Elsa Bazellie ` res and Andre ´ Le Bivic
Abstract
Mechanical forces have emerged as essential regulators of cell organization, proliferation, migration, and
polarity to regulate cellular and tissue homeostasis. Changes in forces or loss of the cellular response to them
can result in abnormal embryonic development and diseases. Over the past two decades, many efforts have
been put in deciphering the molecular mechanisms that convert forces into biochemical signals, allowing
for the identification of many mechanotransducer proteins. Here we discuss how PDZ proteins are
emerging as new mechanotransducer proteins by altering their conformations or localizations upon force
loads, leading to the formation of macromolecular modules tethering the cell membrane to the actin
cytoskeleton.
Key words PDZ proteins, Forces, Tight junctions, Adherens junctions, Actomyosin
1 A Brief Introduction on Mechanotransduction/Mechanoregulation in Biology
All the cells and tissues of the body are subject to external and
internal forces. These forces can affect the shape and intracellular
organization of cells, their proliferation, their migration, and their
intercellular interactions. Forces influence the development of
embryos [1] as well as cell functions and homeostasis in the adult
[2]. Moreover, many disease states are characterized by changes in
these forces and/or a loss of the normal cellular response to them
[3]. Over the last decade, mechanotransduction has emerged as a
key process in development and diseases. Mechanotransduction can
be defined as a cellular event that converts a mechanical input such
as fluid shear stress (blood vessels), stretch (lung, intestine),
osmotic forces (urinary tract), mechanical load (bone, muscle)
[4, 5] as well as the impact of the stiffness of the extracellular matrix
(ECM) that surrounds most cells leading to a biochemical response
[6]. In well-studied examples of mechanotransduction, proteins
can undergo force-induced changes into conformations that lead
to modification in affinity for binding partners or catalytic activity.
The mechanical load triggers biochemical changes that can
Jean-Paul Borg (ed.), PDZ Mediated Interactions: Methods and Protocols, Methods in Molecular Biology, vol. 2256,
https://doi.org/10.1007/978-1-0716-1166-1_15, © Springer Science+Business Media, LLC, part of Springer Nature 2021
257