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.
Muriel
Joaquin M
JM
Program in Cell Structure and Development, Medical Biotechnology Center, University of Maryland Biotechnology Institute, Baltimore, MD 21201, USA.
Dong
Chun
C
Hutter
Harald
H
Vogel
Bruce E
BE
D000009:Abdominal Muscles / Q000254:growth & development / Q000378:metabolism / Q000648:ultrastructure; D017398:Alternative Splicing; D000818:Animals; D001485:Basement Membrane / Q000378:metabolism; D017173:Caenorhabditis elegans / Q000235:genetics / Q000254:growth & development / Q000378:metabolism*; D029742:Caenorhabditis elegans Proteins / Q000235:genetics / Q000502:physiology*; D002135:Calcium-Binding Proteins / Q000235:genetics / Q000502:physiology*; D002448:Cell Adhesion / Q000502:physiology; D048430:Cell Shape / Q000502:physiology; D006066:Gonads / Q000254:growth & development / Q000378:metabolism / Q000648:ultrastructure; D007413:Intestinal Mucosa / Q000378:metabolism; D007422:Intestines / Q000254:growth & development / Q000648:ultrastructure; D008565:Membrane Proteins / Q000235:genetics / Q000502:physiology*; D046529:Microscopy, Electron, Transmission; D009024:Morphogenesis; D009154:Mutation; D010614:Pharynx / Q000254:growth & development / Q000378:metabolism / Q000648:ultrastructure
D029742:Caenorhabditis elegans Proteins; D002135:Calcium-Binding Proteins; D008565:Membrane Proteins; C060820:fibulin; C424064:him-4 protein, C elegans