Temporal and spatial regulation of integrins during development

Abstract

SummaryIntegrin receptors for extracellular matrix (ECM) are critical determinants of biological processes. Regulation of integrin expression is one way for cells to respond to changes in the ECM, to integrate intracellular signals, and to obtain appropriate adhesion for cell motility, proliferation, and differentiation. Transcriptional and post-translational mechanisms for changing the integrin repertoire at the cell surface have recently been described. These mechanisms work through transcriptional regulation that alters the proportions of one integrin relative to another, referred to as integrin switching, or through localized regulation of integrin-ECM interactions, thus providing exquisite control over cell rearrangements during tissue morphogenesis and remodeling. These integrin regulatory pathways may also be important targets in such emerging fields as tissue engineering and regenerative medicine.

Distinct regulatory mechanisms control integrin adhesive processes during tissue morphogenesis

“…Integrin heterodimers, consisting of an a-and b-subunit, span the plasma membrane to form a link between the ECM and the cytoskeleton. Integrins are highly conserved in animals and are essential for vertebrate, fly and worm development (reviewed in Bökel and Brown, 2002;Meighan and Schwarzbauer, 2008). In general, integrin-mediated adhesion contributes to morphogenesis through two mechanisms: dynamic, short-term adhesion to mediate events such as cell migration and cell rearrangement, and stable, long-term adhesion to mediate tissue maintenance (Bökel and Brown, 2002;Meighan and Schwarzbauer, 2008).…”

“…Integrins are highly conserved in animals and are essential for vertebrate, fly and worm development (reviewed in Bökel and Brown, 2002;Meighan and Schwarzbauer, 2008). In general, integrin-mediated adhesion contributes to morphogenesis through two mechanisms: dynamic, short-term adhesion to mediate events such as cell migration and cell rearrangement, and stable, long-term adhesion to mediate tissue maintenance (Bökel and Brown, 2002;Meighan and Schwarzbauer, 2008). During dynamic processes, integrins function in several ways: firstly, they mediate attachment between cells and the ECM, providing traction for cell migration; secondly, integrins act as signaling receptors that regulate cell growth and differentiation; thirdly, integrins contribute to ECM assembly in some tissues (reviewed in Brown et al, 2000;Narasimha and Brown, 2004a).…”

The First Type III Repeat in Fibronectin Activates an Inflammatory Pathway in Dermal Fibroblasts

“…In the present study, we evaluated the effect of the partially unfolded Type III fibronectin module, FnIII Fibronectin is found in the extracellular matrix of most tissues where it functions to support basic cellular processes including cell adhesion, migration, survival, and growth. Fibronectin is a modular protein consisting of independently folded domains, Types I, II, and III, which represent regions of amino acid sequence homology (1). Polymerized fibronectin within the extracellular matrix is subjected to tensional forces generated by the cells that expose cryptic activities within the molecule, including motogenic activity (2), and binding sites for integrins (3)(4)(5) and growth factors (6).…”

Butyrate-induced differentiation of PC12 cells to chromaffin cells involves cell adhesion and induction of extracellular proteins and cell adhesion proteins

“…Integrins are cell surface receptors that transduce outside-in signaling and inside-out signaling (Paschos et al 2009). Integrins are regulated during development (Meighan and Schwarzbauer 2008). During butyrate-induced differentiation of PC12 cells to chromaffin phenotype, integrin beta 1 and alpha 7 were increased (Figure 2A).…”