Rescuing desmoplakin function

Intercellular junctions play an important role not only in structuring the architecture of tissues, but also in integrating mechanical and signaling pathways (reviewed by Barth et al., 1997; Kowalczyk et al., 1999). Most adhering cells form classical adherens junctions, composed of the type of transmembrane receptor of the cadherin superfamily that associates with the actin cytoskeleton (for review, see Barth et al., 1997). However, during development of mammalian embryos, a number of tissues also rely upon a specialized type of calcium-dependent, intercellular adhesion mediated by the link of the intermediate filament (IF) cytoskeleton to other transmembrane receptors of the cadherin superfamily (Kowalczyk et al., 1999). While the precise role(s) of these connections remains undetermined, it has been surmised that the increased stability of the IF network over the actin cytoskeleton may help to provide greater stability to the types of intercellular connections that use this component of the cytoskeleton. This may be particularly important in tissues subjected to considerable mechanical stress, such as heart muscle, skin epidermis and some vascular endothelial structures, all of which feature cadherin-mediated connections to IFs. The most common and robust of the intercellular junctions that use IFs are desmosomes, which are especially abundant in heart muscle and skin epidermis, but not seen in the vasculature. The desmosomal cadherins, desmogleins (Dsgs) and desmocollins (Dscs), form the transmembrane core of the desmosome (Koch and Franke, 1994; Kowalczyk et al., 1999). Specific vascular endothelial cells display unique intercellular junctions that are morphologically and biochemically distinct from either classical adherens junctions or desmosomes. These junctions, referred to as complexus adherens junctions or syndesmos, are composed of the endothelial-specific cadherin, VE-cadherin, rather than desmosomal cadherins (Schmelz and 929 Development 128, 929-941 (2001) Printed in Great Britain © The Company of Biologists Limited 2001 DEV3311