The making of hemidesmosome structures in vivo

Abstract

Hemidesmosomes are evolutionarily conserved attachment complexes linked to intermediate filaments that connect epithelial cells to the extracellular matrix. They provide tissue integrity and resistance to mechanical forces. Alterations in hemidesmosome structures are responsible for skin blistering, carcinoma invasion, and wound-healing defects. Valuable information about hemidesmosome assembly and disassembly has been obtained from in vitro cell culture studies. However, how these processes take place in vivo still remains elusive. Here, we discuss recent data about the formation and reorganization of hemidesmosomes in several in vivo model systems, particularly zebrafish and Caenorhabditis elegans, focusing on various factors affecting their dynamics. Mechanisms found in different organisms reveal that hemidesmosome formation and maintenance in vivo are carefully controlled by ECM protein folding, ECM-receptor expression and trafficking, and by post-translational modification of hemidesmosome components. These findings validate and extend the in vitro studies, and shed light on our understanding about hemidesmosomes across species.

Role of the extracellular matrix in epithelial morphogenesis

“…Like vertebrate HDs, CeHDs contain a plakin protein called VAB-10A, which is closely related to Plectin and BPAG1e. 23 All HD-like components are necessary to reach or go beyond mid-elongation. 23 Our laboratory recently characterized a novel mechanotransduction pathway that accounts, to a large extent, for why muscledeficient embryos cannot elongate.…”

“…23 All HD-like components are necessary to reach or go beyond mid-elongation. 23 Our laboratory recently characterized a novel mechanotransduction pathway that accounts, to a large extent, for why muscledeficient embryos cannot elongate. 24 This pathway involves a tensional input provided by muscle contractions, which are transmitted through the muscle-epidermis BM to induce a mechanotransduction signaling output in the epidermis.…”

“…The BM found at the muscle-epidermis interface contains Perlecan (UNC-52) which acts to anchor muscle myofilaments through integrins, and the epidermis most likely through myotactin (a large single-pass transmembrane nematode specific protein) which organizes C. elegans hemidesmosome-like (CeHD) junction at the basal side of the cell. 23 A distinct set of receptors is found at apical CeHDs (dotted rectangles, right). Muscles are A/P-oriented and anchored to the cuticle through basal and apical CeHDs, which are bridged by intermediate filaments.…”

Separation of distinct adhesion complexes and associated cytoskeleton by a micro-stencil-printing method

“…8,9 Likewise, hemidesmosomes are structured of (1) laminin, (2) integrin associated with plectin and BPAG1e and (3) the intermediate filaments. 10 Generally, it is the specific binding of an extracellular matrix protein to a transmembraneous adhesion complex which dictates the type of the adhesion contacts.…”

Extracellular Matrix in Development: Insights from Mechanisms Conserved between Invertebrates and Vertebrates

“…In insects, the basal junctions contain integrins, but the components of the apical junctions have yet to be discovered. In Caenorhabditis elegans, the basal junctions contain myotactin (and not integrins), whereas two proteins distantly related to matrilins are transmembrane components of apical adhesions (for references see Zhang and Labouesse 2010) The basal ECM of invertebrates shares many components with vertebrate ECMs (see Hynes and Naba 2011;Yurchenco 2011), but also contains novel proteins, e.g., tiggrin in Drosophila (Fogerty et al 1994). The apical ECM (aECM) contains a mixture of components that are unique to invertebrates and those that are conserved with vertebrates (Page and Johnstone 2007;Moussian 2010).…”