Beyond cell-cell adhesion: Emerging roles of the tight junction scaffold ZO-2.

Zonula occludens proteins (ZO-1, ZO-2, ZO-3), which belong to the family of membrane-associated guanylate kinase (MAGUK) homologs, serve as molecular hubs for the assembly of multi-protein networks at the cytoplasmic surface of intercellular contacts in epithelial and endothelial cells. These multi-PDZ proteins exert crucial functions in the structural organization of intercellular contacts and in transducing intracellular signals from the plasma membrane to the nucleus. The junctional MAGUK protein ZO-2 not only associates with the C-terminal PDZ-binding motif of various transmembrane junctional proteins but also transiently targets to the nucleus and interacts with a number of nuclear proteins, thereby modulating gene expression and cell proliferation. Recent evidence suggests that ZO-2 is also involved in stress response and cytoprotective mechanisms, which further highlights the multi-faceted nature of this PDZ domain-containing protein. This review focuses on ZO-2 acting as a molecular scaffold at the cytoplasmic aspect of tight junctions and within the nucleus and discusses additional aspects of its cellular activities. The multitude of proteins interacting with ZO-2 and the heterogeneity of proteins either influencing or being influenced by ZO-2 suggests an exceptional functional capacity of this protein far beyond merely serving as a structural component of cellular junctions.

Distinct modes of vertebrate hypaxial muscle formation contribute to the teleost body wall musculature.

The formation of the body wall musculature in vertebrates is assumed to be initiated by direct ventral extension of the somites/myotomes. This contrasts to the formation of limb muscles and muscles involved in feeding or respiration/ventilation, which are founded by migratory muscle precursors (MMPs) distant to the somites. Here, we present evidence from morphology and expression of molecular markers proposing that the formation of the two muscle layers of the teleost body wall involves both of the above mechanisms: (1) MMPs from somites 5 and 6 found an independent muscle primordium-the so-called posterior hypaxial muscle (PHM)-which subsequently gives rise to the most anterior two segments of the medial obliquus inferioris (OI) muscle. (2) Direct epithelial extension of the hypaxial myotomes generates the OI segments from somite 7 caudalward and the entire lateral obliquus superioris (OS) muscle. The findings are discussed in relation to the evolution of hypaxial myogenic patterning including functional considerations. We hypothesise that the potential of the most anterior somites to generate migratory muscle precursors is a general vertebrate feature that has been differently utilised in the evolution in vertebrate groups.