Evidence for lectin signaling to the nuclear matrix: Cellular interpretation of the glycocode

All cells exist within a context. They are often in contact with other cells or they may be bound by the extracellular matrix (ECM). The microenvironment around a cell, including interactions with neighboring cells and the ECM, has been shown to effect morphology, DNA synthesis, and even gene expression [Gospodarowicz et al., 1978; Bissell et al., 1981]. These signals dictate how a cell responds to its surroundings. In normal tissue, cells are governed by a given set of rules such as contact inhibition and apoptosis, but transformed cells disregard these rules by forming clumps of cells, moving through complex matrices, and ignoring commands for programmed cell death. Understanding what messages cells obtain from their surroundings, how they interpret these messages, and how they respond is an important dynamic of both normal and pathologic cell biology. The tissue matrix is the physical framework connecting the components of a cell with the ECM [Isaacs et al., 1981; Fey et al., 1984; Pienta et al., 1993]. The tissue matrix is a three dimensional structure which links the chromosomes to the nuclear matrix, followed by the cytoskeleton, membrane matrix, and ECM. The nuclear matrix has several functions including determining nuclear morphology [Berezney and Coffey, 1974], providing DNA organization and scaffolding [Pienta et al., 1991], replicating DNA [Vogelstein et al., 1980], and transcribing RNA as well as directing RNA transport [Ciejek et al., 1982]. The cytoskeletal matrix is composed of intermediate ®laments (IFs), actin micro®laments, and microtubules and plays a role in cytokinesis and mitosis. IFs speci®cally have been shown to provide direct contact between the nuclear matrix and the cytoskeleton. A cell interacts with its microenvironment through the membrane matrix, proteins and glycoproteins imbedded in the plasma membrane. Protein±protein interactions have been shown to be an important component not only for cellular adhesion, but also for signal transduction. Cell surface integrins, a family of heterodimeric glycoproteins, have been well described as binding to speci®c RGD sequences found in collagen and other membrane proteins [Ruoslahti and Obrink, 1996; Gahmberg et al., 1997]. The cytoplasmic domains of integrins have been shown to bind to essential cytoskeletal proteins such as talin and a-actinin, and activate focal adhesion kinase in creating adhesion complexes. By interacting with the ECM and neighboring cells through the adhesive properties of its external domain, and the cytoskeletal framework with its cytoplasmic domain, integrins demonstrate an ability to bridge the gap between mechanical adhesion and intracellular signaling. While much focus in the ®eld of cell adhesion and ECM interactions has been placed on integrins and protein±protein interactions, we are only just beginning to understand the spectrum of protein±carbohydrate interactions. Breaking the DNA and polypeptide codes has allowed the in-depth study of the passage of genetic material, mutations of this system, and its expression into proteins. Both DNA and polypeptides represent linear codes with permutations of a limited set of units. Carbohydrates, by containing branched chains and additional sulfate, phosphate, or O-acetyl groups, have a variety of organizational