RRC ID 45530
著者 Blanchette CR, Perrat PN, Thackeray A, Bénard CY.
タイトル Glypican Is a Modulator of Netrin-Mediated Axon Guidance.
ジャーナル PLoS Biol
Abstract Netrin is a key axon guidance cue that orients axon growth during neural circuit formation. However, the mechanisms regulating netrin and its receptors in the extracellular milieu are largely unknown. Here we demonstrate that in Caenorhabditis elegans, LON-2/glypican, a heparan sulfate proteoglycan, modulates UNC-6/netrin signaling and may do this through interactions with the UNC-40/DCC receptor. We show that developing axons misorient in the absence of LON-2/glypican when the SLT-1/slit guidance pathway is compromised and that LON-2/glypican functions in both the attractive and repulsive UNC-6/netrin pathways. We find that the core LON-2/glypican protein, lacking its heparan sulfate chains, and secreted forms of LON-2/glypican are functional in axon guidance. We also find that LON-2/glypican functions from the epidermal substrate cells to guide axons, and we provide evidence that LON-2/glypican associates with UNC-40/DCC receptor-expressing cells. We propose that LON-2/glypican acts as a modulator of UNC-40/DCC-mediated guidance to fine-tune axonal responses to UNC-6/netrin signals during migration.
巻・号 13(7)
ページ e1002183
公開日 2015-7-1
DOI 10.1371/journal.pbio.1002183
PII PBIOLOGY-D-15-00685
PMID 26148345
PMC PMC4493048
MeSH Animals Axons / physiology* Caenorhabditis elegans Caenorhabditis elegans Proteins / metabolism* Glypicans / metabolism* Nerve Tissue Proteins / metabolism* Netrins Signal Transduction Syndecans / metabolism
IF 7.076
引用数 17
WOS 分野 BIOLOGY BIOCHEMISTRY & MOLECULAR BIOLOGY
リソース情報
線虫 tm595 tm2051