Biomedical subjects

Chun Dong

Publications and source records attributed to Chun Dong.

4 recordsLinked to original sources

PubMed2006

Hemicentins assemble on diverse epithelia in the mouse.

Hemicentins are recently described extracellular matrix (ECM) proteins with a single ortholog in C. elegans that assembles into discrete tracks constricting broad regions of epithelial cell contact into adhesive and flexible line-shaped junctions. There are two highly conserved hemicentin genes in most vertebrate species; however, nothing is known about the function or distribution of vertebrate hemicentins. To determine the distribution of vertebrate hemicentins, we used a polyclonal antibody to stain mouse tissue and showed that hemicentins are found in the pericellular ECM of epithelial cells in a number of tissues including embryonic trophectoderm and adult skin and tongue, in addition to the ECM of some, but not all, blood vessels. Hemicentins also assemble on multiple epithelia in the eye, including cornea, lens, and retina. The pericellular localization of vertebrate hemicentins on epithelia and other cell surfaces suggests that vertebrate hemicentins, like their nematode counterpart, are secreted ECM proteins likely to have a role in the architecture of adhesive and flexible cell junctions, particularly in tissues subject to significant amounts of mechanical stress.

Amino Acid Sequence↗

PubMed2006

Hemicentin assembly in the extracellular matrix is mediated by distinct structural modules.

Hemicentins are conserved extracellular matrix proteins characterized by a single von Willebrand A (VWA) domain at the amino terminus, a long stretch (>40) of tandem immunoglobulin domains, multiple tandem epidermal growth factors (EGFs), and a single fibulin-like carboxyl-terminal module. In Caenorhabditis elegans, hemicentin is secreted from muscle and gonadal leader cells and assembles at multiple locations into discrete tracks that constrict broad regions of cell contact into adhesive and flexible line-shaped junctions. To determine hemicentin domains critical for function and assembly, we have expressed fragments of hemicentin as GFP tagged fusion proteins in C. elegans. We find that a hemicentin fragment containing the VWA domain can target to multiple assembly sites when expressed under the control of either endogenous hemicentin regulatory sequences or the muscle-specific unc-54 promoter. A hemicentin fragment containing the EGF and fibulin-like carboxyl-terminal modules can co-assemble with existing hemicentin polymers in wild-type animals but has no detectable function in the absence of endogenous hemicentin. The data suggest that the VWA domain is a cell binding domain whose function is to target hemicentin to sites of assembly and the EGF/fibulin-like carboxyl-terminal modules constitute an assembly domain that mediates direct interactions between hemicentin monomers during the hemicentin assembly process.

Animals↗

PubMed2006

Hemicentins: what have we learned from worms?

Hemicentins are conserved extracellular matrix proteins discovered in Caenorhabditis elegans, with orthologs in all vertebrate species including human and mouse. Hemicentins share a single, highly conserved amino-terminal von Willebrand A domain, followed by a long (>40) stretch of immunoglobulin repeats, multiple tandem epidermal growth factors and a fibulin-like carboxy-terminal module. C. elegans has a single hemicentin gene that has pleiotropic functions in transient cell contacts that are required for cell migration and basement membrane invasion and in stable contacts at hemidesmosome-mediated cell junctions and elastic fiber-like structures. Here, we summarize what is known about the function of hemicentin in C. elegans and discuss implications for hemicentin function in other species.

Animals↗

PubMed2005

Fibulin-1C and Fibulin-1D splice variants have distinct functions and assemble in a hemicentin-dependent manner.

Fibulins are a family of extracellular glycoproteins associated with basement membranes and elastic fibers in vertebrates. Conservation of the fibulin-1 gene throughout metazoan evolution includes fibulin-1C and fibulin-1D alternate splice variants, although little is known about variant specific functions that would justify this striking structural conservation. We have therefore investigated the structure, localization and loss-of-function phenotype specific to both fibulin-1 variants in C. elegans. We find that fibulin-1C has specific roles during pharynx, intestine, gonad and muscle morphogenesis, being required to regulate cell shape and adhesion, whereas fibulin-1D assembles in flexible polymers that connect the pharynx and body-wall-muscle basement membranes. The assembly of fibulin-1C and fibulin-1D in multiple locations is dependent upon the presence of hemicentin, a recently described extracellular member of the immunoglobulin superfamily. We suggest that the distinct developmental roles and hemicentin-dependent assembly for fibulin-1 splice variants demonstrated here may be relevant to fibulin-1 and possibly other fibulin family members in non-nematode species.

Abdominal Muscles↗