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Phenotypes

Mouse phenotype:

increased circulating alanine transaminase level

Subcellular localization

cilia, Golgi apparatus, Vesicles

Functional category

• Non-motile cilium / primary cilium
• Trafficking (BBSome
• small GTPases
• vesicular transport
• ATPases)
• Signaling (Hedgehog
• GPCRs
• ion channels)
• Ciliary assembly/disassembly

Function

Glypican-6 (GPC6), a heparan sulfate proteoglycan, is highly expressed in SHH-MB. In this study, we demonstrate the synchronous expression of GPC6 with GLI1 in both the developing cerebellum and medulloblastoma. GPC6 promoted the cell proliferation, migration, and invasion in SHH-MB cell lines (DAOY and ONS-76). Consistently, GPC6 enhanced SHH pathway activity by upregulating GLI1 expression, supported ciliogenesis that is essential for signal transduction, and facilitated the secretion of SHH ligands via extracellular vesicles. These findings establish GPC6 as a critical regulator of SHH-MB progression and highlight its potential as a therapeutic target(41320180). In this study, we show that GPC6-null embryos display most of the abnormalities found in OMOD1 patients and that Hedgehog (Hh) signaling is significantly reduced in the long bones of these embryos. The Hh-stimulatory activity of GPC6 was also observed in cultured cells, where this GPC increased the binding of Hh to Patched 1 (Ptc1). Consistent with this, GPC6 interacts with Hh through its core protein and with Ptc1 through its glycosaminoglycan chains. Hh signaling is triggered at the primary cilium. In the absence of Hh, we observed that GPC6 is localized outside of the cilium but moves into the cilium upon the addition of Hh. We conclude that GPC6 stimulates Hh signaling by binding to Hh and Ptc1 at the cilium and increasing the interaction of the receptor and ligand(28696225).