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 m ajor heparan sulfate proteoglycan of the extracellular matrix. This is a la rge complex protein with regions similar to low-density lipoprotein recepto rs, laminin, and neural cell adhesion molecules (NCAMs). In this study, we extend our earlier work and demonstrate that a number of complex isoforms o f this protein are expressed through alternative splicing. We identified th ree major classes of perlecan isoforms: a short form lacking the NCAM regio n and the C-terminal agrin-like region; a medium form containing the NCAM r egion, 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 sp atial and temporal expression pattern for these UNC-52 isoforms. As well, u sing a series of mutations affecting different regions and thus different i soforms 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 atta chment, and their role in development remains unclear.