Selective assembly of fibulin‐1 splice variants reveals distinct extracellular matrix networks and novel functions for perlecan/UNC‐52 splice variants

Abstract

Fibulin-1C and fibulin-1D splice variants have been conserved throughout metazoan evolution and have distinct functions in Caenorhabditis elegans development. Both splice variants are required for the assembly of hemidesmosome-mediated mechanosensory neuron and uterine attachments, although the molecular associations that underlie their distinct functions at these locations are not known. Here, we show that the assembly of fibulin-1C and fibulin-1D splice variants at these anchorages is dependent upon distinct components of the extracellular matrix (ECM): Fibulin-1D assembly at uterine and mechanosensory neurons attachments is dependent upon a perlecan/ UNC-52 splice variant that includes alternately spliced IG8-IG10, whereas the assembly of fibulin-1C at mechanosensory neuron attachments is dependent upon laminin/ EPI-1. These data not only indicate that fibulin-1C and fibulin-1D are components of distinct networks of ECM but also demonstrates a novel function for a major class of perlecan splice variants found in C. elegans and mouse. In addition, we demonstrate that overexpression of another ECM protein, collagen XVIII, can suppress gonad morphogenesis defects associated with loss of fibulin-1C, suggesting that some genetic defects that result in a weakened basement membrane can be compensated by overexpression of genes for ECM components that stabilize basement membranes.

Molecular evolution of the fibulins: Implications on the functionality of the elastic fibulins

“…Eumetazoans possess a complex embryonary development that gives rise to differentiated tissue layers and which is dependent on the presence of a complex ECM that serves as the medium for cell migration, cell-cell communication, and reservoir of growth factor substances (Morris, 1993). A Eumetazoan origin is supported by the roles of FBLNs in protostomes like C. elegans, where they associate with the basement membrane and regulate cell adhesion processes (Hesselson et al, 2004;Kubota et al, 2004;Muriel et al, 2006;Vogel et al, 2006).…”

Fibulins: Multiple roles in matrix structures and tissue functions

“…Fibulin-1D assembles in the flexible polymers that connect the pharynx and body wall muscle. Both isoforms requires fibulin-6 (hemicentin) for assembly at hemidesmosomes-mediated mechanosensory neuron and uterine attachments to the epidermis [90]. In addition, assembly of fibulin-1C at uterine and mechanosensory neuron attachments is depend on perlecan, whereas assembly of fibulin-1D at mechanosensory neuron attachments is dependent on laminin [90].…”

A new role for laminins as modulators of protein toxicity in Caenorhabditis elegans

“…S4) different from EV. Fibulin binds to laminins and nidogens of the BM (Kramer 2005) and the assembly of fbl-1 at mechanosensory neuron attachments is dependent on epi-1 (Muriel et al 2006) , which may explain the observed effect on paralysis. Similarly, dystroglycan is a receptor for epi-1 (Johnson et al 2006).…”