Complex patterns of alternative splicing mediate the spatial and temporal distribution of perlecan/UNC-52 in Caenorhabditis elegans

The unc-52 gene encodes the nematode homologue of mammalian perlecan, the major heparan sulfate proteoglycan of the extracellular matrix. This is a large complex protein with regions similar to low-density lipoprotein receptors, laminin, and neural cell adhesion molecules (NCAMs). In this study, we...

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Published in:	Molecular biology of the cell Vol. 10; no. 10; pp. 3205 - 3221
Main Authors:	Mullen, G P, Rogalski, T M, Bush, J A, Gorji, P R, Moerman, D G
Format:	Journal Article
Language:	English
Published:	United States The American Society for Cell Biology 01-10-1999
Subjects:	Agrin - chemistry Alternative Splicing Amino Acid Sequence Animals Caenorhabditis elegans - embryology Caenorhabditis elegans - genetics Caenorhabditis elegans Proteins Cloning, Molecular Disorders of Sex Development Fluorescent Antibody Technique Gene Expression Regulation, Developmental Helminth Proteins - genetics Helminth Proteins - metabolism Heparan Sulfate Proteoglycans Heparitin Sulfate - genetics Heparitin Sulfate - metabolism Membrane Proteins Microscopy, Confocal Molecular Sequence Data Muscle Development Mutation Neural Cell Adhesion Molecules - chemistry Protein Isoforms Proteoglycans - genetics Proteoglycans - metabolism Sequence Alignment Sequence Deletion
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Summary:	The unc-52 gene encodes the nematode homologue of mammalian perlecan, the major heparan sulfate proteoglycan of the extracellular matrix. This is a large complex protein with regions similar to low-density lipoprotein receptors, laminin, and neural cell adhesion molecules (NCAMs). In this study, we extend our earlier work and demonstrate that a number of complex isoforms of this protein are expressed through alternative splicing. We identified three major classes of perlecan isoforms: a short form lacking the NCAM region and the C-terminal agrin-like region; a medium form containing the NCAM region, but still lacking the agrin-like region; and a newly identified long form that contains all five domains present in mammalian perlecan. Using region-specific antibodies and unc-52 mutants, we reveal a complex spatial and temporal expression pattern for these UNC-52 isoforms. As well, using a series of mutations affecting different regions and thus different isoforms of UNC-52, we demonstrate that the medium NCAM-containing isoforms are sufficient for myofilament lattice assembly in developing nematode body-wall muscle. Neither short isoforms nor isoforms containing the C-terminal agrin-like region are essential for sarcomere assembly or muscle cell attachment, and their role in development remains unclear.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 Corresponding author. E-mail address: moerman@zoology.ubc.ca.
ISSN:	1059-1524 1939-4586
DOI:	10.1091/mbc.10.10.3205