Proteoglycan Puts Growths Factors in the Right Place at the Right Time

Abstract

A migrating cell is often confronted with a multitude of environmental cues--it is challenged with integrating disparate signals and then harnessing the appropriate cellular machinery to move in the desired direction. Movement of the distal tip cells (DTCs) in Caenorhabditis elegans larva during gonad development has provided insights into how extracellular matrix components regulate cell adhesion and motility. The ventral-to-dorsal migration stage of DTCs is regulated by UNC-6, a member of the netrin family of secreted guidance cues, and their membrane receptors, UNC-5 and UNC-40. In a series of genetic modifier screens, Merz et al. have identified a basement membrane heparan sulfate proteoglycan (HSPG) called UNC-52, a homolog of perlecan, that also affects this stage of DTC migration. Studies in other organisms have described perlecan function as both a structural basement membrane protein and as a regulator of growth factor signaling. Defects in unc-52 alone did not affect DTC migration, but exacerbated migration defects of some unc-5 hypomorphs. The authors observed suppression of the ability of unc-52 mutant alleles to enhance unc-5 DTC defects by additional loss-of-function mutations in certain growth factor-encoding genes. These results suggest that UNC-52 is a basal lamina protein that may localize and control accessibility of growth factors that affect DTC migration. D. C. Merz, G. Alves, T. Kawano, H. Zheng, J. G. Cylotti, UNC-52/Perlecan affects gonadal leader cell migrations in C. elegans hermaphrodites through alterations in growth factor signaling. Dev. Biol. 256, 173-186 (2003). [Online Journal]