Faculty Collaboration Database

Coordination of Heparan Sulfate Proteoglycans with Wnt Signaling To Control Cellular Migrations and Positioning in Caenorhabditis elegans. Genetics 2017 Aug;206(4):1951-1967

Date

06/04/2017

Pubmed ID

28576860

Pubmed Central ID

PMC5560800

DOI

10.1534/genetics.116.198739

Scopus ID

2-s2.0-85027049485 (requires institutional sign-in at Scopus site)   21 Citations

Abstract

Heparan sulfates (HS) are linear polysaccharides with complex modification patterns, which are covalently bound via conserved attachment sites to core proteins to form heparan sulfate proteoglycans (HSPGs). HSPGs regulate many aspects of the development and function of the nervous system, including cell migration, morphology, and network connectivity. HSPGs function as cofactors for multiple signaling pathways, including the Wnt-signaling molecules and their Frizzled receptors. To investigate the functional interactions among the HSPG and Wnt networks, we conducted genetic analyses of each, and also between these networks using five cellular migrations in the nematode Caenorhabditis elegans We find that HSPG core proteins act genetically in a combinatorial fashion dependent on the cellular contexts. Double mutant analyses reveal distinct redundancies among HSPGs for different migration events, and different cellular migrations require distinct heparan sulfate modification patterns. Our studies reveal that the transmembrane HSPG SDN-1/Syndecan functions within the migrating cell to promote cellular migrations, while the GPI-linked LON-2/Glypican functions cell nonautonomously to establish the final cellular position. Genetic analyses with the Wnt-signaling system show that (1) a given HSPG can act with different Wnts and Frizzled receptors, and that (2) a given Wnt/Frizzled pair acts with different HSPGs in a context-dependent manner. Lastly, we find that distinct HSPG and Wnt/Frizzled combinations serve separate functions to promote cellular migration and establish position of specific neurons. Our studies suggest that HSPGs use structurally diverse glycans in coordination with Wnt-signaling pathways to control multiple cellular behaviors, including cellular and axonal migrations and, cellular positioning.

Author List

Saied-Santiago K, Townley RA, Attonito JD, da Cunha DS, Díaz-Balzac CA, Tecle E, Bülow HE

Author

Eillen Tecle PhD Assistant Professor in the Microbiology and Immunology department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Animals
Axon Guidance
Caenorhabditis elegans
Caenorhabditis elegans Proteins
Cell Movement
Frizzled Receptors
Glypicans
Neurons
Syndecans
Wnt Signaling Pathway