Communication between the cell membrane and the nucleus: Role of protein compartmentalization

Abstract

Understanding how the information is conveyed from outside to inside the cell is a critical challenge for all biologists involved in signal transduction. The flow of information initiated by cell-cell and cell-extracellular matrix contacts is mediated by the formation of adhesion complexes involving multiple proteins. Inside adhesion complexes, connective membrane skeleton (CMS) proteins are signal transducers that bind to adhesion molecules, organize the cytoskeleton, and initiate biochemical cascades. Adhesion complex-mediated signal transduction ultimately directs the formation of supramolecular structures in the cell nucleus, as illustrated by the establishment of multi complexes of DNA-bound transcription factors, and the redistribution of nuclear structural proteins to form nuclear subdomains. Recently, several CMS proteins have been observed to travel to the cell nucleus, suggesting a distinctive role for these proteins in signal transduction. This review focuses on the nuclear translocation of structural signal transducers of the membrane skeleton and also extends our analysis to possible translocation of resident nuclear proteins to the membrane skeleton. This leads us to envision the communication between spatially distant cellular compartments (i.e., membrane skeleton and cell nucleus) as a bidirectional flow of information (a dynamic reciprocity) based on subtle multilevel structural and biochemical equilibria. At one level, it is mediated by the interaction between structural signal transducers and their binding partners, at another level it may be mediated by the balance and integration of signal transducers in different cellular compartments.

Signaling Properties of Hyaluronan Receptors

“…2). In this case, hyaladherins such as RHAMM could contribute to the back and forth flow of information between the cell genome and the extracellular environment, a phenomenon that has been termed "dynamic reciprocity" (51). For instance, RHAMM modules could represent a modified version of "inside-outside" signaling characteristic of integrin receptors (52).…”

Tissue Polarity-Dependent Control of Mammary Epithelial Homeostasis and Cancer Development: an Epigenetic Perspective

“…Many epigenetic factors have multiple engagements; they can be found in an extranuclear compartment in parallel to their nuclear location, and either shuttle between cytoplasm and nucleus or become free from their cytoplasmic location to travel to the cell nucleus upon specific signals [2]. Signal transducers trapped within the cell cortex may be released upon alteration of cell adhesion complexes and then, trigger pathways that influence gene transcription; however, an increasing body of literature is reporting that scaffold proteins that participate in the making of cell adhesion complexes might also directly impact gene transcription by traveling to the cell nucleus.…”

The Likely Role of Proteolytic Enzymes in Unwanted Differentiation of Stem Cells in Culture

“…The environmental changes are transmitted to the cells through the connection between the surface proteins on the cell surface and these ECM proteins [9,10]. Thus, the interactions between mammalian cells and ECM occur via surface proteins.…”

“…The interplay between the right balance of formation and loss of these complexes as well as the different types of adhesion molecules in each cell forms a key combination for tissue development, maintenance and differentiation [9]. …”

“…This 3D culture presented specific components of breast tissue environment. Those cells returned to a normal like organizational morphology and function (producing milk) [9,17]. Thus, the cell can no longer be thought of as a lone entity defined by their genome, but it must be evaluated in the ECM context, soluble growth factors, hormones and other small molecules that regulate organs and functions.…”